Maternal Stressful Life Events During the Periconceptional Period and Orofacial Clefts: A Systematic Review and Meta-Analysis

Objective To assess whether women who experience stressful life events during the periconceptional period are at higher risk of giving birth to a baby with an orofacial cleft (OFC). Design Systematic review and meta-analysis of studies reporting the proportion of babies born with OFC to mothers exposed and unexposed to population-level or personal-level stressful life events during the periconceptional period. Six electronic databases were searched from inception to August 2020. Risk of bias was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) for the odds of OFC in babies of exposed mothers relative to unexposed controls were extracted and/or calculated. Random effects meta-analysis was undertaken, stratified by cleft subtype. Results Of 12 eligible studies, 8 examined experience of personal events and 4 examined population-level events. Studies demonstrated low-moderate risk of bias and there was indication of publication bias. There was some evidence that personal stressful life events were associated with greater odds of cleft lip and/or palate (six studies, OR 1.63, 95% confidence interval (CI) 1.16, 2.30, P = 0.001) and cleft palate only (six studies, OR 1.45, 95% CI 1.02, 2.06, P = 0.04). Population-level events were associated with higher odds of OFC in studies that did not specify subtype (three studies, OR 1.64, 95% CI 1.19, 2.25, P = 0.002), but subtype stratified analyses were underpowered. Heterogeneity was high. Conclusions Limited evidence indicated a weak positive association between maternal stressful life events during the periconceptional period and risk of OFC in the offspring, but further studies with greater consistency in research design are needed.

Maternal One-carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.

Consequences of Paternal Nutrition on Offspring Health and Disease

It is well established that the maternal diet during the periconceptional period affects the progeny’s health. A growing body of evidence suggests that the paternal diet also influences disease onset in offspring. For many years, sperm was considered only to contribute half of the progeny’s genome. It now appears that it also plays a crucial role in health and disease in offspring’s adult life. The nutritional status and environmental exposure of fathers during their childhood and/or the periconceptional period have significant transgenerational consequences. This review aims to describe the effects of various human and rodent paternal feeding patterns on progeny’s metabolism and health, including fasting or intermittent fasting, low-protein and folic acid deficient food, and overnutrition in high-fat and high-sugar diets. The impact on pregnancy outcome, metabolic pathways, and chronic disease onset will be described. The biological and epigenetic mechanisms underlying the transmission from fathers to their progeny will be discussed. All these data provide evidence of the impact of paternal nutrition on progeny health which could lead to preventive diet recommendations for future fathers.

The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

Incidence of neural tube defects and their risk factors within a cohort of Moroccan newborn infants

Background Neural tube defects (NTDs) are a group of birth defects that result from a partial or complete failure of the neural tube to close during embryogenesis. Their prevalence varies between 0.5 to 2 per 1000 births in countries without folic acid supplementation. The aim of our study is to assess the NTDs incidence and describe the risk factors within Moroccan newborn infants. Method This is a descriptive study over a period of 5 and a half years including all births at “Les Orangers” Maternity and Reproductive Health Hospital of Rabat with notification of NTD cases, whether isolated or combined with other anomalies. Data were reported on pre-established sheets and on the teratovigilance registry. Statistical analysis was performed with SPSS version 18 statistical software. Results During the study period, 43,923 births were recorded including 44 cases of neural tube defects, an incidence rate of 1 per 1000 births, with a female predominance; sex ratio = 0.8. These defects included anencephaly (50%), spina bifida (38.6%) and encephalocele (11.4%). The risk factors detected during this study include consanguinity (34%), consumption of fenugreek or other plants (36%), diabetes (4.5%) and medication (2.2%). A family history of malformation was reported in 6.8% of cases and among siblings in 4.5% of cases. The average maternal age was 30.38 ± 6.88 and the average gestational age was 36.80 ± 5.11. A quarter of mothers did not benefit from any medical monitoring during pregnancy while 59% did not take folic acid supplementation during the first trimester of pregnancy and none of them took B9 vitamin during the periconceptional period. The antenatal diagnosis was performed in 63% of cases. The mortality rate was 3.8 per 10,000 and 16% of cases evolved positively. Conclusion NTDs require high intensity and multidisciplinary care which stresses the importance, in our context, of strengthening and optimizing acid folic supplementation strategies during the periconceptional period.

Vaccination Status of Mothers and Children from the ‘Mamma & Bambino’ Cohort

According to the evidence demonstrating vaccines’ safety and effectiveness in anticipation of and during pregnancy, several countries have established immunization programs during the periconceptional period. Here, we evaluated vaccination status among 220 mother–child pairs, using data from the ‘Mamma & Bambino’ cohort. The self-reported data were evaluated at delivery, and with planned follow-ups at 1–2 years after delivery. In general, we noted that the vaccination status among the women was heterogeneous, ranging from 8.3% (vaccine against Human Papillomavirus, HPV) to 65.6% (vaccine against Diphtheria Tetanus and Pertussis, DTaP). Excluding the women who contracted the diseases in the past, the main ground for refusal was the lack of information. We also demonstrated that increasing age was associated with higher odds of not being vaccinated against Measles-Mumps-Rubella (MMR; OR = 1.12; 95% CI = 1.04–1.21; p = 0.004), HPV (OR = 1.20; 95% CI = 1.08–1.33; p = 0.001) and DTaP (OR =1.09; 95% CI = 1.01–1.18; p = 0.040). As expected, we showed that the proportion of newborns vaccinated with the Hexavalent and Pneumococcal vaccines was high (99.5% and 98.6%, respectively), while the vaccination coverage against MMRV did not reach the auspicated threshold (84.1%). Overall, these results underlined the need for the improvement of women’s knowledge about the recommendations for vaccination, especially during pregnancy.

Effects of maternal nutrient restriction during the periconceptional period on placental development in the mouse

Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic disease risks during adulthood. The placenta is responsible for transport of nutrients from the maternal to fetal circulation, and the efficiency with which it does so can be adjusted to the maternal nutrient supply. There is evidence that placental adaptations to nutrient restriction in early pregnancy may be retained even when adequate nutrition is restored later in pregnancy, leading to a potential mismatch between placental efficiency and maternal nutrient supplies. However, in the mouse, 50% caloric restriction from days 1.5–11.5 of gestation, while temporarily altering placental structure and gene expression, had no significant effect on day 18.5. The periconceptional period, during which oocyte maturation, fertilization, and preimplantation development occur may be especially critical in creating lasting impact on the placenta. Here, mice were subjected to 50% caloric restriction from 3 weeks prior to pregnancy through d11.5, and then placental structure, the expression of key nutrient transporters, and global DNA methylation levels were examined at gestation d18.5. Prior exposure to caloric restriction increased maternal blood space area, but decreased expression of the key System A amino acid transporter Slc38a4 at d18.5. Neither placental and fetal weights, nor placental DNA methylation levels were affected. Thus, total caloric restriction beginning in the periconceptional period does have a lasting impact on placental development in the mouse, but without changing placental efficiency.

A CASE REPORT ON IMPACT OF PRE-GESTATIONAL DIABETES MELLITUS ON PREGNANCY OUTCOME IN A WOMEN WITH BAD OBSTETRIC HISTORY

Background Perinatal and neonatal mortality remains a challenge in the care of pregnant women worldwide, particularly for those who had a history of adverse outcome in previous pregnancies. Bad Obstetric History implies previous unfavorable fetal outcome in terms of two or more consecutive spontaneous abortion, H/O intrauterine fetal death, intrauterine growth restriction, stillbirth, early neonatal death and/or congenital anomalies. Age, obesity and high parity have been shown to be independent risk factors for recurrent pregnancy loss and stillbirths. About 3 to 10% of pregnancies are complicated by glycemic control abnormalities. The main underlying cause is lethal embryonic malformations due to glucose teratogenicity at high levels if diabetes is poorly controlled in the periconceptional period and first trimester.

Micronutrient provision in a woman during pregravid preparation, pregnancy and breastfeeding. Challenges and prospects

Adequate micronutrient provision in a woman at the stage of pregravid preparation, during pregnancy is very important for its normal course, as well as for the well-being of the woman and her future offspring. In the periconceptional period, throughout pregnancy, as well as during breastfeeding, the need for a number of micronutrients increases. A balanced diet can compensate for it only to some extent, given that in our country there is a deficiency of micronutrients which are essential for the normal course of pregnancy, and the need for their supplement remains from the preconceptional period until the end of lactation. Excessive intake of vitamins carries certain risks: long-term administration of multicomponent vitamin-mineral complexes is associated with an increase in the risk of fetal macrosomia, and as the number of their components increases, so does the probability of pharmaceutical and pharmacokinetic interactions between them. The desire to reach the optimal dosage of one of the components with its true hypovitaminosis can lead to a violation of the dosage of its other components. Thus, nutritional support during pregnancy requires a basic supplement of strictly defined vitamins and microelements essential for normal gestation, such as folic acid, iodine, vitamin D and polyunsaturated fatty acids at dosages corresponding to the daily physiological requirement established for pregnant women. Key words: pregnancy, vitamins, vitamin D, iodine, lactation, micronutrients, polyunsaturated fatty acids, pregravid preparation, folates