BACKGROUND: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature.
OBJECTIVE: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols.
METHODS: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies.
RESULTS: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47).
CONCLUSIONS: The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.

The present umbrella review evaluated the environmental risk factors prior to conception associated with fetal macrosomia based on meta-analyses and systematic reviews. We systematically searched international databases, including PubMed, Scopus, and Web of Science, until April 2023 by using some relevant keywords. The quality of the included studies was assessed using the AMSTAR 2checklist. The risk factor of advanced maternal age 35-39 years compared with <30 years (OR 1·42, 95 % CI: 1·25, 1·60), prepregnancy obesity (OR 1.93, 95 % CI: 1.65, 2.27) and excessive weight gain before and during pregnancy (OR 2.35, 95 % CI: 1.95, 2.85) were graded as suggestive evidence (class III). Two risk factors of advanced maternal age >40 years compared with <30 years (OR 1.40, 95 % CI: 1.02, 1.78) and gestational diabetes mellitus (GDM) without insulin use (OR 1.70, 95 % CI: 1.23, 2.36) were graded as risk factors with weak evidence (class IV). Advanced maternal age, prepregnancy obesity, excessive weight gain before and during pregnancy, and GDM without insulin use were environmental risk factors for macrosomia.

UNASSIGNED: Cell-free fetal DNA (cffDNA) is a novel screening method for fetal aneuploidy that facilitated non-invasive prenatal testing (NIPT) through analysis of cffDNA in maternal plasma. However, despite increased sensitivity, it has a number of limitations that may complicate of its results interpretation. Therefore, elucidating factors affecting fetal fraction, as a critical limitation, guides its clinical application.
UNASSIGNED: In this report, systematic search was carried out through PubMed, Web of Science, and Scopus databases until February 11, 2022 by using keywords consist of \"noninvasive prenatal screening\", \"NIPT\", \"noninvasive prenatal\", \"cell free DNA\" and \"fetal fraction\". The articles were screened for eligibility criteria before data extraction.
UNASSIGNED: A total of 39 eligible studies, most published between 2010 and 2020, were included. Based on the results of studies, a negative correlation between maternal age and BMI/body weight with fetal fraction was found. Furthermore, LDL, cholesterol, triglyceride level, metformin, heparin and enoxaparin therapy, hemoglobin-related hemoglobinopathies, and physical activity showed to have negative associations. Interestingly, it seems the ethnicity of patients from South and East Asia has a correlation with fetal fraction compared to Caucasians. Positive correlation was observed between gestational age, free β-hCG, PAPP-A, living in high altitude, and twin pregnancy.
UNASSIGNED: Considering each factor, there was significant inconsistency and controversy regarding their impact on outcomes. Indeed, multiple factors can influence the accuracy of NIPS results, and it is worth noting that the impact of these factors may vary depending on the individual\'s ethnic background. Therefore, it is important to recognize that NIPS remains a screening test, and comprehensive pre- and post-NIPS counseling should be conducted as part of standard clinical practice.

UNASSIGNED: This systematic review aimed to understand the impact of advanced maternal age (AMA) on the neonatal morbidity, based on the available scientific evidence.
UNASSIGNED: A systematic search was conducted on 22 November 2021, using the PubMed and Scopus databases to identify studies that compared the morbidity of neonates delivered to AMA mothers with that of neonates delivered to non-AMA mothers.
UNASSIGNED: Sixteen studies that evaluated the effect of AMA on the neonatal morbidity were included in this review. Nine of these studies found some association between AMA and increased neonatal morbidity (with two of them only reporting an increase in asymptomatic hypoglycemia, and one only reporting an association in twins), six found no association between AMA and neonatal morbidity and one study found a decrease in morbidity in preterm neonates. The studies that found an increase in overall neonatal morbidity with AMA considered older ages for the definition of AMA, particularly ≥40 and ≥45 years.
UNASSIGNED: The current evidence seems to support a lack of association between AMA and the neonatal morbidity of the delivered neonates. However, more studies focusing on the neonatal outcomes of AMA pregnancies are needed to better understand this topic.

Preeclampsia is a serious condition that is linked to poor perinatal outcomes. In Ethiopia, the overall prevalence of preeclampsia and its associated factors is uncertain. Therefore, the purpose of this review was to find the prevalence of pre-eclampsia and its determinants in Ethiopia.
To find primary studies, PubMed, Google Scholar, HINAR, Scopus, the Web of Sciences, and grey literature searches were used between January 1, 2013, and January 1, 2023, in Ethiopia. A Microsoft Excel sheet was used to extract data. The pooled prevalence of pre-eclampsia was predicted using a random-effect model.
Twenty-nine studies were included. The pooled prevalence of pre-eclampsia was 11.51% (95% CI: 8.41, 14.61). Age > 35 years old (AOR = 2.34, 95%CI, 1.74-2.94; p-value = 0.64), housewife (AOR = 2.76, 95%CI, 1.2-4.32; p-value = 0.37), previous history of pre-eclampsia (AOR = 4.02, 95%CI, 2.91-5.55; p-value = 0.09), family history of hypertension (OR = 1.84, 95%CI, 1.39-2.3; p-value = 0.4), history of chronic hypertension (AOR = 2.44, 95%CI, 1.8-3.08; p-value = 0.67), history of multiple pregnancies (AOR = 1.45, 95%CI, 1.09-1.8; p-value = 0.38), and alcohol intake during pregnancy (AOR = 1.53, 95%CI, 1.03-2.04; p-value = 0.03) were the determinants of pre-eclampsia.
When compared to previous studies, the overall pooled prevalence of pre-eclampsia was high. Pre-eclampsia is associated with maternal age >35 years, being a housewife, having a history of preeclampsia, having a history of chronic hypertension, having a family history of hypertension, having diabetes mellitus, drinking alcohol during pregnancy, and having multiple pregnancies.

UNASSIGNED: Previous studies evaluating the relationship between blood manganese (Mn) level and gestational diabetes mellitus (GDM) in pregnant women showed inconsistent results. A systematic review and meta-analysis was therefore performed to investigate the above association.
UNASSIGNED: Relevant observational studies were obtained by search of electronic databases including Medline, Embase, Cochrane Library and Web of Science from database inception to 10 March 2023. Two authors independently performed database search, literature identification and data extraction. A randomised-effects model was selected to pool the data by incorporating the influence of potential heterogeneity. Subgroup analysis was performed to evaluate the influence of study characteristics on the results of the meta-analysis.
UNASSIGNED: Six datasets from five observational studies, involving 91,249 pregnant women were included in the meta-analysis. Among the participants, 3597 (3.9%) were diagnosed as GDM. Overall, pooled results showed that a high blood level of Mn was associated with a higher risk of GDM (compared between women with highest versus lowest category blood Mn, odds ratio: 1.31, 95% confidence interval: 1.19-1.44, p < .001) with no significant heterogeneity (p for Cochrane Q-test = 0.93, I2 = 0%). Subgroup analyses according to study design, mean maternal age, matrix or methods for measuring blood Mn, and the incidence of GDM also showed consistent results (p for subgroup difference all >.05).
UNASSIGNED: Results of the meta-analysis suggest that a high blood Mn level may be a risk factor of GDM in pregnant women. Studies are needed to determine the underlying mechanisms, and to investigate if the relationship between blood Mn level and GDM is dose-dependent.
Changes of blood manganese (Mn) have been suggested to be involved in the pathogenesis of diabetes. However, the relationship between blood Mn level and gestational diabetes mellitus (GDM) in pregnant women remains undetermined. Our study represents the first systematic review and meta-analysis to investigate the potential association between blood Mn concentration and the risk of GDM. In this meta-analysis, we pooled the results of six datasets from five observational and showed that compared to pregnant women with the lowest category of blood Mn level, those with the highest category of blood Mn level were associated with a higher risk of GDM. These results suggest that a high blood concentration of Mn in pregnant women may be a risk factor of GDM.

The health of the mother and children are potentially affected by several types of cultural malpractices that occur during the perinatal period. Ethiopia is a multi-ethnic nation where a variety of cultural practices are observed, especially during pregnancy, delivery, and the postpartum period. This study aimed to assess the prevalence and associated factors of cultural malpractice during the perinatal period in Ethiopia. Data searches were conducted in PubMed/Medline, Web of Science, Scopus, Google Scholar, African Journals Online, and the Cochrane Library. Data were extracted using Microsoft Excel, and analysis was done using STATA version 14. Less than a p-value of 0.05 was regarded to indicate potential publication bias: the funnel plot, Begg, and Egger\'s regression tests were used to examine publication bias. This study included 18 studies and 7880 mothers. The pooled prevalence of cultural malpractice during pregnancy, childbirth, and postpartum was 34.95% (95% CI: 27, 42.56), 31.18% (95% CI: 19.61, 42.76), and 45.83% (95% CI: 34.22, 57.45) respectively in Ethiopia. In addition, the following factors are statistically associated with the perinatal period: pregnancy: ANC follow-up (AOR = 3.06, 95%CI = 2.04, 4.58), educational status (AOR = 3.30, 95%CI = 1.99, 5.48), and residence (AOR 2.47, 95%CI, 1.601, 3.81); childbirth: ANC follow-up (AOR = 9.94, 95%CI = 2.05, 48.09), maternal age (AOR = 2.27, 95%CI = 1.56, 3.29), and maternal education (AOR = 10.37, 95%CI = 6.145, 17.51); during postpartum: ANC follow-up (AOR = 3.67, 95%CI = 1.96, 6.844), maternal education (AOR = 6.87, 95%CI = 3.26, 14.49), and residence AOR4.79, 95%CI, 2.97, 7.49). The pooled prevalence of cultural malpractice during the perinatal period was high. Health professionals should encourage beneficial practices through health education for a healthy perinatal period for mothers.

OBJECTIVE: Most pregnant people take at least one medication during gestation or while breastfeeding, however data are lacking on the safety of medication use in these populations. We conducted a landscape review of real-world data sources specific to medication use in pregnancy and breastfeeding populations that have met, or have potential to meet, health authorities\' requirements for post-authorization safety studies.
METHODS: A 2-phase approach identified data sources from literature, publicly available registers of non-interventional post-authorization studies of pregnant women, existing database inventories, and emerging data sources known to the authors.
RESULTS: Required key attributes were assessed according to current regulatory guidance, resulting in selection of 49 suitable data sources. All global regions were represented, with North America (37%) and Europe (33%) most common; 12% of the data sources included pregnancy information from low-to middle-income countries. Administrative healthcare claims (25%) and electronic healthcare records (21%) comprised the largest types of data sources. Across data sources, 53% were managed by national or regional governments, 27% by industry, and 20% by academic institutions. Maternal age, diagnoses, prenatal care, and reproductive history were available in most, whereas fewer included demographic data (e.g., race/ethnicity). Breastfeeding data were collected in 37% of the final data sources.
CONCLUSIONS: We conducted a systematic approach to data source evaluation of pregnancy and breastfeeding to be used as a resource for investigators to consider when designing pregnancy-related research studies to satisfy regulatory requirements.

Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA.
Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.

A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development.
Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated.
Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight.
The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.