Initiatives to optimise preconception health are emerging following growing recognition that this may improve the health and well-being of women and men of reproductive age and optimise health in their children. To inform and evaluate such initiatives, guidance is required on indicators that describe and monitor population-level preconception health. We searched relevant databases and websites (March 2021) to identify national and international preconception guidelines, recommendations and policy reports. These were reviewed to identify preconception indicators. Indicators were aligned with a measure describing the prevalence of the indicator as recorded in national population-based data sources in England. From 22 documents reviewed, we identified 66 indicators across 12 domains. Domains included wider (social/economic) determinants of health; health care; reproductive health and family planning; health behaviours; environmental exposures; cervical screening; immunisation and infections; mental health, physical health; medication and genetic risk. Sixty-five of the 66 indicators were reported in at least one national routine health data set, survey or cohort study. A measure of preconception health assessment and care was not identified in any current national data source. Perspectives from three (healthcare) professionals described how indicator assessment and monitoring may influence patient care and inform awareness campaign development. This review forms the foundation for developing a national surveillance system for preconception health in England. The identified indicators can be assessed using national data sources to determine the population’s preconception needs, improve patient care, inform and evaluate new campaigns and interventions and enhance accountability from responsible agencies to improve preconception health.

Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.

Prenatal exposure to nicotine, tobacco’s major addictive constituent, has been shown to reduce birth weight and increases apoptosis, oxidative stress, and mitochondrial dysfunction in the postnatal pancreas. Given that upregulated levels of the pro-oxidative adapter protein p66shc is observed in growth-restricted offspring and is linked to beta-cell apoptosis, the goal of this study was to investigate whether alterations in p66shc expression underlie the pancreatic deficits in nicotine-exposed offspring. Maternal administration of nicotine in rats increased p66shc expression in the neonatal pancreas. Similarly, nicotine treatment augmented p66shc expression in INS-1E pancreatic beta cells. Increased p66shc expression was also associated with decreased histone H3 lysine 9 methylation. Finally, nicotine increased the expression of Kdm4c, a key histone lysine demethylase, and decreased Suv39h1, a critical histone lysine methyltransferase. Collectively, these results suggest that upregulation of p66shc through posttranslational histone modifications may underlie the reported adverse outcomes of nicotine exposure on pancreatic function.

Evidence suggests that maternal prepregnancy body mass index (BMI) is associated with offspring cardiometabolic risk factors. This study was aimed at assessing the association of maternal prepregnancy BMI with offspring cardiometabolic risk factors in adolescence and adulthood. We also evaluated whether offspring BMI was a mediator in this association. The study included mother–offspring pairs from three Pelotas birth cohorts. Offspring cardiometabolic risk factors were collected in the last follow-up of each cohort [mean age (in years) 30.2, 22.6, 10.9]. Blood pressure was measured using an automatic device, cholesterol by using an enzymatic colorimetric method, and glucose from fingertip blood, using a portable glucose meter. In a pooled analysis of the cohorts, multiple linear regression was used to control for confounding. Mediation analysis was conducted using G-computation formula. In the adjusted model, mean systolic blood pressure of offspring from overweight and obese mothers was on average 1.25 (95% CI: 0.45; 2.05) and 2.13 (95% CI: 0.66; 3.59) mmHg higher than that of offspring from normal-weight mothers; for diastolic blood pressure, the means were 0.80 (95% CI: 0.26; 1.34) and 2.60 (95% CI: 1.62; 3.59) mmHg higher, respectively. Non-HDL cholesterol was positively associated with maternal BMI, whereas blood glucose was not associated. Mediation analyses showed that offspring BMI explained completely the association of maternal prepregnancy BMI with offspring systolic and diastolic blood pressure, and non-HDL cholesterol. Our findings suggest that maternal prepregnancy BMI is positively associated with offspring blood pressure, and blood lipids, and this association is explained by offspring BMI.

Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001–0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.

The benefits of consuming soy and its protein have been reported in many studies. However, its phytoestrogen content raises concerns about consumption during lactation and gestation We therefore examined the effects of soybean or soy protein isolate on the parameters-related cardiovascular pathophysiology in lactating mothers and their offsprings at weaning and adulthood. Lactating rats were divided: casein control (C); soy protein isolate (SPI); and soybean (S). At weaning, half of the litter received commercial ration up to 150 days. The levels of 17-β-estradiol and superoxide dismutase were low in the S mothers. For the SPI mothers, we observed a reduction of thiobarbituric acid reactive substances (TBARS). At weaning, atherogenic indices [1 = total cholesterol (TC)/HDL; 2 = LDL/HDL; 3 = TC-HDL/HDL)] decreased in the S and SPI offsprings compared to the casein control group; TBARS and antioxidant enzymes increased in the S offspring, while reduced/oxidized glutathione ratio increased in the SPI offspring, indicating lower oxidative stress. In adulthood, the SPI offspring showed an increase in liver cholesterol and atherogenic index 1 and 3 (vs. C and S) and 2 (vs. S). In addition, we found a decrease in catecholamines in the adrenal medulla and an increase in caffeine-stimulated secretion, but tyrosine hydroxylase expression remained constant. Maternal consumption of SPI during lactation worsened atherogenic indices of the offsprings in adulthood, which was associated with increased liver cholesterol and decreased catecholamines in the adrenal medulla. Soy consumption had no consistent long-term effects on the evaluated parameters compared to casein consumption. The data suggest that the consumption of SPI during lactation should be done with caution.

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.

Infant neurodevelopment is a complex process which may be affected by different events during pregnancy, such as hypertensive disorders of pregnancy (HDP). We conducted a prospective cohort study to compare the prevalence of neurodevelopmental disorders in infants born to mothers with and without HDP at six months of age. Participants attended the Health Observatory of Instituto de Desarrollo e Investigaciones Pediátricas “Prof. Dr. Fernando E. Viteri” during 2018 and 2019. Infant neurodevelopment was assessed with the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III). Data were analyzed using Chi-square, Student’s t-test and Mann–Whitney test. Of the 132 participating infants, 68 and 64 were born to mothers with and without HDP, respectively. At six months, the prevalence of risk of neurodevelopmental delay was significantly higher in infants born to mothers with than without HDP (27.9% vs. 9.4%; p = 0.008) (odds ratio, 3.71; 95% confidence interval, 1.30; 12.28). In conclusion, infants born to mothers with HDP had three times increased risk of neurodevelopmental delay at six months of age.

Maternal exercise has shown beneficial effects on mother and child. Literature confirm progeny’s cognition improvement, and upregulation in neurotrophins, antioxidant network, and DNA repair system. Considering that there is a lack of information demonstrating the impact of maternal exercise on offspring’s skeletal muscle, we aimed to investigate the mitochondrial and redox effects elicited by maternal swimming. Adult female Wistar rats were divided into three groups: control sedentary, free swimming, and swimming with overload (2% of the body weight). Exercised groups were submitted weekly to five swimming sessions (30 min/day), starting 1 week prior to the mating and lasting to the delivery. Gastrocnemius and soleus muscle from 60-day-old offspring were analyzed. Our results clearly showed a sex-dependent effect. Male soleus showed increased mitochondrial functionality in the overload group. Female muscle from the overload group adapted deeply. Considering the redox status, the female offspring delivered to overload exercised dams presented reduced oxidants levels and protein damage, allied to downregulated antioxidant defenses. We also observed an increase in the mitochondrial function in the gastrocnemius muscle of the female offspring born from overload exercised dams. Soleus from female delivered to the overload exercise group presented reduced mitochondrial activity, as well as reduced reactive species, protein carbonyls, and antioxidant network, when compared to the male. In conclusion, maternal exercise altered the redox status and mitochondrial function in the offspring’s skeletal muscle in a sex-dependent way. The clinical implication was not investigated; however, the sexual dimorphism in response to maternal exercise might impact exercise resilience in adulthood.

Intrauterine undernutrition may lead to fetal vascular programming. We compared abdominal aortic intima-media thickness (aIMT) and aortic diameter (aD) between appropriate for gestational age (AGA) and growth-restricted fetuses (GRF). We recruited 136 singleton fetuses at 34–37 weeks of gestation from Fetal Medicine Unit of Aga Khan University Hospital, Karachi (January–November 2017). Subjects were classified as AGA (n = 102) and GRF (n = 34) using INTER-GROWTH 21st growth reference and standard ultrasound protocol. Their far- and near-wall aIMT and aD were compared after adjustment of maternal age, first-trimester body mass index, fetal gender, hypertension and hyperglycemia in pregnancy. As the severity of growth restriction increased in GRF, aIMT and aD showed an increasing and a decreasing trend, respectively. Both far- and near-wall aIMT in GRF [(adj. β = 0.082, 95% confidence interval [CI] 0.042–0.123) and (adj. β = 0.049, 95% CI 0.010–0.089)] were significantly greater with reference to AGA fetuses. GRF subgroup analysis into small for gestational age (SGA) fetuses and intrauterine growth restricted (IUGR) revealed highly significant difference between AGA and IUGR for far (0.142 mm, P-value < 0.001) and near-wall aIMT (0.115 mm, P-value < 0.001) and marginally significant aD difference (0.51 mm, P-value 0.05). These findings suggest that the extent of fetal aortic remodelling is influenced by the severity of growth restriction. Hence, the targeted interventions for the cardiovascular health promotion of IUGR and SGA born neonates are desirable during early childhood, particularly in set ups with high prevalence of low birth weight babies.

While donor-conceived children have similar mental health outcomes compared to spontaneously conceived children, there is an inconsistency between studies investigating mental health outcomes of donor-conceived people in adulthood. This study is an online health survey that was completed by 272 donor sperm-conceived adults and 877 spontaneously conceived adults from around the world. Donor sperm-conceived adults had increased diagnoses of attention deficit disorder (P = 0.004), and autism (P = 0.044) in comparison to those conceived spontaneously. Donor sperm-conceived adults self-reported increased incidences of seeing a mental health professional (P < 0.001), identity formation problems (P < 0.001), learning difficulties (P < 0.001), panic attacks (P = 0.038), recurrent nightmares (sperm P = 0.038), and alcohol/drug dependency (P = 0.037). DASS-21 analysis revealed that donor sperm-conceived adults were also more stressed than those conceived spontaneously (P = 0.013). Both donor sperm and spontaneously conceived cohorts were matched for sex, age, height, alcohol consumption, smoking, exercise, own fertility, and maternal smoking. The increase in adverse mental health outcomes is consistent with some studies of donor-conceived adult mental health outcomes. These results are also consistent with the Developmental Origins of Health and Disease (DOHaD) phenomenon that has linked adverse perinatal outcomes, which have been observed in donor-conceived neonates, to increased risk of chronic disease, including mental health. Further work is required to reconcile our observations in adults to contrary observations reported in donor-conceived children.

Maternal nutrition is critical in mammalian development, influencing the epigenetic reprogramming of gametes, embryos, and fetal programming. We evaluated the effects of different levels of sulfur (S) and cobalt (Co) in the maternal diet throughout the pre- and periconceptional periods on the biochemical and reproductive parameters of the donors and the DNA methylome of the progeny in Bos indicus cattle. The low-S/Co group differed from the control with respect to homocysteine, folic acid, B12, insulin growth factor 1, and glucose. The oocyte yield was lower in heifers from the low S/Co group than that in the control heifers. Embryos from the low-S/Co group exhibited 2320 differentially methylated regions (DMRs) across the genome compared with the control embryos. We also characterized candidate DMRs linked to the DNMT1 and DNMT3B genes in the blood and sperm cells of the adult progeny. A DMR located in DNMT1 that was identified in embryos remained differentially methylated in the sperm of the progeny from the low-S/Co group. Therefore, we associated changes in specific compounds in the maternal diet with DNA methylation modifications in the progeny. Our results help to elucidate the impact of maternal nutrition on epigenetic reprogramming in livestock, opening new avenues of research to study the effect of disturbed epigenetic patterns in early life on health and fertility in adulthood. Considering that cattle are physiologically similar to humans with respect to gestational length, our study may serve as a model for studies related to the developmental origin of health and disease in humans.

The effects of supraphysiological estradiol (E2) on neonatal outcomes and the significance of specific E2 concentrations remain unclear. The purpose of this study was to investigate whether supraphysiological E2 levels on the human chorionic gonadotropin (hCG) trigger day are associated with small size for gestational age (SGA) in singletons born from fresh embryo transfer (ET) cycles. Patients with singleton pregnancies who delivered after the transfer of fresh embryos, during the period from July 2012 to December 2017, at our center were included. We excluded cycles involving a vanishing twin, maternal age >35 years, basal follicle-stimulating hormone ≥10 mIU/ml, or anti-Müllerian hormone ≤1 ng/ml. We then divided all cycles into five groups by E2 level on trigger day: group A, <2000 pg/ml (reference group); group B, 2000 pg/ml≤E2<2999 pg/ml; group C, 3000 pg/ml≤E2<3999 pg/ml; group D, 4000 pg/ml≤E2<4999 pg/ml; and group E, ≥5000 pg/ml. The prevalence of SGA among singletons from fresh ET was the primary outcome. The SGA rate significantly increased when the E2 level was ≥4000 pg/ml, as observed by comparing groups D (odds ratio [OR]: 1·79, 95% confidence interval [CI]: 1·16–2·76, P = 0·01) and E (OR: 1·68, 95% CI: 1·10–2·56, P = 0·02) with the reference group. Multivariate logistic regression indicated that a serum E2 level of at least 4000 pg/ml on the hCG trigger day was associated with increased SGA and with significant differences for groups D (adjusted OR [AOR]: 1·65, 95% CI: 1·05–2·59, P = 0·03) and E (AOR: 1·60, 95% CI: 1·03–2·53, P = 0·04) relative to the reference group. In conclusion, in fresh ET cycles, the supraphysiological E2 ≥4000 pg/ml on the hCG trigger day increases the risk of SGA.

Nicotine is the main psychoactive substance present in cigarette smoke that is transferred to the baby by breast milk. In rats, maternal nicotine exposure during breastfeeding induces obesogenesis and hormone dysfunctions in adult male offspring. As glucocorticoid (GC), insulin, and vitamin D change both adipogenesis and lipogenesis processes, we assessed parameters related to metabolism and action of these hormones in visceral and subcutaneous adipose tissues (VAT and SAT) of adult male and female rats in a model of neonatal nicotine exposure. At postnatal (PN) day 2, dams were kept with six pups (three per sex) and divided into nicotine and control groups for implantation of osmotic minipumps that released 6 mg/kg nicotine or saline, respectively. At PN180, fat mass, hormone levels, and protein contents of biomarkers of the GC activation and receptor (11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor alpha), insulin signaling pathway [insulin receptor beta (IRβ), phosphorylated insulin receptor substrate 1, insulin receptor substrate 1 (IRS1), phosphorylated serine/threonine kinase (pAKT), serine/threonine kinase, glucose transporter type 4 (GLUT4)], and vitamin D activation and receptor (1α-hydroxylase and vitamin D receptor) were evaluated. While nicotine-exposed males showed increased fat mass, hypercorticosteronemia, hyperinsulinemia, and higher 25-hydroxyvitamin D, these alterations were not observed in nicotine-exposed females. Nicotine-exposed males only showed lower IRS1 in VAT, while the females had hyperglycemia, higher pAKT in VAT, while lower IRβ, IRS1, and GLUT4 in SAT. Parameters related to metabolism and action of GC and vitamin D were unaltered in both sexes. We evidence that exposure exclusively to nicotine during breastfeeding affects the hormone status and fat depots of the adult progeny in a sex-dependent manner.

Maternal obesity increases the risk of nonalcoholic fatty liver disease (NAFLD) in offspring. The Roux-en-Y gastric bypass (RYBG) is effective for achieving weight loss and ameliorates NAFLD. To determine whether these benefits are maintained after pregnancy and/or lactation, and whether they modulate hepatic morphofunction in the next generation, we evaluated hepatic lipid metabolism in Western diet (WD)-obese female rats that underwent RYGB and in their F1 offspring at adulthood. Female Wistar rats consumed a WD from 21 to 130 days of age, before being submitted to RYGB (WD-RYGB-F0) or SHAM (WD-SHAM-F0) operations. After 5 weeks, these females were mated with control male breeders, and the male and female F1 offspring were identified as WD-RYGB-F1 and WD-SHAM-F1. WD-RYGB-F0 dams exhibited lower serum lipids levels, but severe hepatic steatosis and pathological features of advanced liver injury. The hepatic proteins involved in lipogenesis were reduced in WD-RYGB-F0, as were the genes related to β-oxidation and bile acids (BAs). Although the female and male WD-RYGB-F1 groups did not exhibit hepatic steatosis, the livers of female WD-RYGB-F1 demonstrated higher amounts of lipogenic genes and proteins, while male WD-RYGB-F1 presented a similar downregulation of lipogenic factors to that seen in WD-RYGB-F0 dams. In contrast, maternal and offspring groups of both sexes displayed reductions in the expressions of genes involved in BAs physiology and gluconeogenesis. As such, RYGB aggravates NAFLD after pregnancy and lactation and induces a gender-dependent differential expression of the hepatic lipogenesis pathway in offspring, indicating that female WD-RYGB-F1 may be an increased risk of developing NAFLD.