Periconceptional Use Research Articles

Periconceptional Supplementation with Folic Acid or Multiple Micronutrients Containing Folic Acid and the Risk for Hypertensive Disorders in Pregnancy

Objective: The aim of this study was to investigate the association between supplementation containing folic acid only (FAO) or multiple micronutrients containing folic acid and the risk for hypertensive disorders in pregnancy (HDP). Subjects and Methods: The retrospective cohort study was based on data from women who gave birth from 2016 to 2018 at Tongzhou Maternal and Child Health Care Hospital of Beijing, China. The outcomes were HDP diagnosed after the 20th week of pregnancy, including gestational hypertension (GH), preeclampsia, and eclampsia. Associations between supplementation patterns and HDP were estimated by Poisson loglinear regression models. Sensitivity analyses were based on prepregnancy body mass index (BMI) and maternal age. Results: Among the 25,866 women included in the study, periconceptional use of FA supplementation marginally reduced the risk for HDP (adjusted risk ratio [aRR] = 0.87, 95% confidence interval [CI] 0.73–1.04). Women who began FAO supplementation before conception had a lower risk for GH compared to those who began after conception (aRR = 0.59, 95% CI: 0.45–0.78). The risk for HDP also reduced among FAO users who began supplementation before conception with a normal prepregnancy BMI (aRR = 0.64, 95% CI: 0.49–0.84) and users ≥30 years old (aRR = 0.75, 95% CI: 0.58–0.98). Conclusions: Periconceptional FAO supplementation may reduce the risk for HDP, especially GH. The protective effects are greater among women with a normal prepregnancy BMI and those ≥30 years old.

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Is periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population? Women with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA. Periconceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA. A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020. We included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires. This study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA. Following the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS. Our findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended. This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest. NTR4356.

Folic acid supplements and perinatal mortality in China.

Periconceptional use of multivitamins containing folic acid prevents external major birth defects, especially neural tube defects. We aimed to explore the effects of maternal folic acid supplementation alone on perinatal mortality with or without external major birth defects plus neural tube defects. From the China-US Collaborative Project for Neural Tube Defects Prevention, we identified 222, 303 singleton pregnancies with detailed information on periconceptional folic acid use, defined as folic acid supplementary before the last menstrual date until to the end of the first trimester. Perinatal mortality included stillbirths after 20 weeks' gestation and early neonatal deaths within 7 days of delivery. Among the fetuses or infants of women who did not take folic acid, the rate of perinatal mortality was 2.99% and 1.62% at least 20 weeks' gestation in the northern and southern regions. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.85% and 1.39% in the northern and southern region. The estimated relative risk for perinatal mortality [adjusted risk ratio (RR), 0.72; 95% confidence interval (CI), 0.61- 0.85], stillbirth (adjusted RR, 0.78; 95% CI, 0.64-0.96), early neonatal mortality (adjusted RR, 0.61; 95% CI, 0.45-0.82), and neonatal death (adjusted RR, 0.64; 95% CI, 0.49-0.83) in northern China was significantly decreased in association with periconceptional folic acid supplementation. Compared with northern, there was a lesser effect in southern China. Periconceptional intake of 400μg folic acid daily reduces the overall risk perinatal mortality, as well as the risk from external major birth defects and neural tube defects, especially in northern China.

Awareness of Periconceptional use of Folic Acid to Prevent Neural Tube Defects in Young Females of Dakshina Kannada Region, India: A Cross-sectional Study

Introduction: Neural Tube Defects (NTDs) are one of the common congenital anomalies leading to miscarriages and serious disabilities in newborns. NTDs are the second most common type of birth defects. Even though the aetiology of NTDs is multifactorial, Folic Acid (FA) deficiency is the most common cause. There are limited Indian studies on awareness of FA usage in the general public. Aim: To assess the awareness and usage of FA to prevent NTDs in young ladies of Mangaluru, Dakshina Kannada (DK) district, Karnataka, India. Materials and Methods: It was a community-based crosssectional study conducted at Father Muller Medical College in Dakshina Kannada district, Mangaluru, Dakshina Kannada (DK) district, Karnataka, India from August 2023 to October 2023. A total of 300 young Indian females aged 18-35 years, residing in the study district, were randomly chosen as participants. Data were collected by an interviewer using a semistructured questionnaire with two components. Part 1 focused on sociodemographic details, while Part 2 gathered information on the awareness of FA supplements, dietary sources of FA, the best time, and dosage of FA supplements to prevent NTDs. Descriptive analysis of the data was done. Results: The study included 90 married and 210 unmarried females. The average age of the participants was 23.7±5.7 years. The study results observed that only 103 (34%) of the participants had heard about FA supplements. A total of 240 (80%) of them said they were not aware of the preferred time for FA. Only 9 (3%) females could mention the correct dose of FA. Conclusion: The study results indicate a gross lack of awareness about FA supplements to prevent NTDs in the general population of the region.

Periconceptional folic acid usage and its associated factors in eastern Sudan: A cross-sectional study.

Several countries poorly adhere to the World Health Organization's recommendation of folic acid supplementation in the periconceptional period, especially in limited-resource settings. The objective of this study was to investigate the prevalence of and the factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital in eastern Sudan. This is a cross-sectional study. This study was conducted in eastern Sudan from April to September 2022. A total of 720 pregnant women in their first trimester were enrolled. The sociodemographic characteristics and clinical and obstetrical data of pregnant women in their first trimester were assessed using a face-to-face questionnaire. In addition, multivariate regression analysis was performed. In this study, the median (interquartile range) of the age and gravidity of the enrolled women was 26.3 (24.14-29.52) years and 2 (1-4), respectively. Of these 720 women, 423 (58.8%) used folic acid during the periconceptional period, while 27 (3.7%) women used folic acid in the preconceptional period. None of the investigated factors (age, residence, education, employment, body mass index, or gravidity) were associated with periconceptional use of folic acid. The study revealed a low prevalence of folic acid usage in preconceptional period among pregnant women in eastern Sudan. Additional efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.

Knowledge and Practices on Periconceptional use of Folic Acid for the Prevention of Neural Tube Defects Among Women in Childbearing Age in Boralesgamuwa Medical Officer of Health Area, Sri Lanka

Introduction: Neural Tube Defects (NTD) remain a major public health burden globally. It is widely acknowledged that folic acid plays a vital role to reduce the risk of developing NTDs. The study aimed to determine knowledge, and practice regarding periconceptional use of folic acid for the prevention of NTD among women in childbearing age at Boralesgamuwa Medical Officer of Health (MOH) area, Sri Lanka.Methods: A descriptive cross-sectional study was carried out among randomly selected 422 women in childbearing age in the said MOH area. Data were collected through a pre-tested interviewer administered questionnaire. The overall knowledge level was classified as adequate (&gt;75%), moderately adequate (50-75%) and inadequate (&lt;50%).Results: Out of 422 participants, the majority was Sinhalese (95.7%), married (66.8%) and unemployed (62.1%). Mean age was 32.02 ±8.625 years. Nearly 56 % had heard about NTDs and 95.5% had heard about folic acid. A majority (279, 66.1%) had ‘inadequate’ level of knowledge, 120 (28.4%) had ‘moderately adequate’ knowledge and only 5.5% (n=23) had ‘adequate’ knowledge. Approximately 60% had taken folic acid and out of them only 42.4% had started folic acid before pregnancy. Age (p&lt;0.001), marital status (p&lt;0.001), parity (p&lt;0.001), educational qualification of participants (p&lt;0.001), monthly household income (p=0.004) and where health services sought from (p &lt;0.001) were associated with the level of knowledge.Conclusions: Majority of participants had inadequate knowledge regarding periconceptional use of folic acid for the prevention of NTDs. However, out of those who have used FA, majority had started to take it before pregnancy. The study findings warrant more educational programmes on the topic bridging the gap of knowledge among women in childbearing age in the study setting.

Folic acid supplementation use during the peri-conceptional period among professionals of a hospital in France

Folic acid insufficiency is an important risk factor for congenital neural tube defects. Despite recommendations and national campaigns, the proportion of women taking folic acid in the peri-conceptional period remains insufficient worldwide. We describe in this study the proportion of peri-conceptional folic acid supplementation use and its determinants among a population of hospital workers during the course of a prevention campaign. We performed a single-center cross sectional study in a university hospital in France. Data were collected during 2 months in 2019 by an online questionnaire sent to all professionals. We collected information about folic acid supplementation use, its modalities (form, period, frequency and dosage) and reason for initiating or not supplementation. Response rate was 11.4 % (n = 1,075/9,447). Among the 748 women who reported at least one pregnancy, 72.7 % (95 % CI: 69.4–76.0 %) reported taking folic acid during their last pregnancy. Main reason for initiating supplementation was information given by a health professional (87.8 %), especially by gynaecologists-obstetricians. Principal factors associated with folic acid supplementation use were age between 25 and 35 years, high level of education and recent pregnancy. Folic acid supplementation use is still not systematic before and during pregnancy, even among health professionals. There is a case for mandatory folic acid fortification for the French general population.

Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy

Increasing use of second-line noninsulin antidiabetic medication (ADM) in pregnant individuals with type 2 diabetes (T2D) may result in fetal exposure, but their teratogenic risk is unknown. To evaluate periconceptional use of second-line noninsulin ADMs and whether it is associated with increased risk of major congenital malformations (MCMs) in the infant. This observational population-based cohort study used data from 4 Nordic countries (2009-2020), the US MarketScan Database (2012-2021), and the Israeli Maccabi Health Services database (2009-2020). Pregnant women with T2D were identified and their live-born infants were followed until up to 1 year after birth. Periconceptional exposure was defined as 1 or more prescription fill of sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, or insulin (active comparator) from 90 days before pregnancy to end of first trimester. Relative risks (RRs) and 95% CIs for MCMs were estimated using log-binomial regression models, adjusting for key confounders in each cohort and meta-analyzed. Periconceptional exposure to second-line noninsulin ADMs differed between countries (32, 295, and 73 per 100 000 pregnancies in the Nordics, US, and Israel, respectively), and increased over the study period, especially in the US. The standardized prevalence of MCMs was 3.7% in all infants (n = 3 514 865), 5.3% in the infants born to women with T2D (n = 51 826), and among infants exposed to sulfonylureas was 9.7% (n = 1362); DPP-4 inhibitors, 6.1% (n = 687); GLP-1 receptor agonists, 8.3% (n = 938); SGLT2 inhibitors, 7.0% (n = 335); and insulin, 7.8% (n = 5078). Compared with insulin, adjusted RRs for MCMs were 1.18 (95% CI, 0.94-1.48), 0.83 (95% CI, 0.64-1.06), 0.95 (95% CI, 0.72-1.26), and 0.98 (95% CI, 0.65-1.46) for infants exposed to sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors, respectively. Use of second-line noninsulin ADMs is rapidly increasing for treatment of T2D and other indications, resulting in an increasing number of exposed pregnancies. Although some estimates were imprecise, results did not indicate a large increased risk of MCMs above the risk conferred by maternal T2D requiring second-line treatment. Although reassuring, confirmation from other studies is needed, and continuous monitoring will provide more precise estimates as data accumulate.

Methotrexate use among men—association with fertility and the perinatal health of their children: a Swedish nationwide register study

To study the effect of methotrexate on male fertility and subsequent effects on their children, for which data are scarce and contradictory. Nationwide multiregister cohort study. Not applicable. All children born alive in Sweden between 2006 and 2014 and their fathers. Three cohorts were defined: children to fathers with periconceptional methotrexate exposure (exposed cohort), children whose fathers stopped methotrexate intake ≥2 years before conception (previously exposed cohort), and children to fathers with no methotrexate exposure (control cohort). The father having at least one dispensed methotrexate prescription from pharmacies 0-3 months before conception, along with at least one more dispensed methotrexate prescription 0-12 months before conception (periconceptional exposure). Previously exposed cohort: the father having no dispensed methotrexate prescriptions in the 2 years before conception, but having at least two dispensed prescriptions before that. Congenital anomalies (major and any; primary outcomes), preterm birth (PTB) and being small for gestational age (SGA; secondary outcomes), as well as need of intracytoplasmic sperm injection (ICSI) to achieve pregnancy (primary outcome in exposed cohort vs. controls, exploratory outcome in previously exposed cohort vs. controls). Outcomes were analyzed using logistic regression. A total of 223 children to fathers with periconceptional methotrexate exposure were identified, along with 356 children whose fathers stopped methotrexate intake ≥2 years before conception and 809,706 not methotrexate-treated controls. In children with fathers periconceptionally exposed to methotrexate, the adjusted and unadjusted odds ratios (95% confidence intervals) for major congenital anomalies were 1.1 (0.4-2.6) and 1.1 (0.4-2.4), any congenital anomalies 1.3 (0.7-2.4) and 1.4 (0.7-2.3), PTB 1.0 (0.5-1.8) and 1.0 (0.5-1.8), SGA 1.1 (0.4-2.6) and 1.0 (0.4-2.2), and conception by use of ICSI 3.9 (2.2-7.1) and 4.6 (2.5-7.7). Use of ICSI was not increased among fathers who stopped methotrexate intake ≥2 years before conception, having adjusted and unadjusted odds ratios 0.9 (0.4-1.9) and 1.5 (0.6-2.9). This study suggests that paternal periconceptional methotrexate use does not increase risk of congenital anomalies, PTB, or SGA in the offspring but may temporarily reduce fertility.

Associations of periconceptional oral contraceptive use with pregnancy complications and adverse birth outcomes.

Periconceptional use of oral contraceptives (OCs) has been reported to increase risks of pregnancy complications and adverse birth outcomes, but risks are suggested to differ depending on the timing of discontinuation, amount of oestrogen and progestin content. Prospective cohort study among 6470 pregnancies included in the PRegnancy and Infant DEvelopment (PRIDE) Study in 2012-19. Exposure was defined as any reported use of OCs within 12 months pre-pregnancy or after conception. Outcomes of interest were gestational diabetes, gestational hypertension, pre-eclampsia, pre-term birth, low birthweight and small for gestational age (SGA). Multivariable Poisson regression using stabilized inverse probability weighting estimated relative risks (RRs) with 95% CIs. Any periconceptional OC use was associated with increased risks of pre-eclampsia (RR 1.38, 95% CI 0.99-1.93), pre-term birth (RR 1.38, 95% CI 1.09-1.75) and low birthweight (RR 1.45, 95% CI 1.10-1.92), but not with gestational hypertension (RR 1.09, 95% CI 0.91-1.31), gestational diabetes (RR 1.02, 95% CI 0.77-1.36) and SGA (RR 0.96, 95% CI 0.75-1.21). Associations with pre-eclampsia were strongest for discontinuation 0-3 months pre-pregnancy, for OCs containing ≥30 µg oestrogen and for first- or second-generation OCs. Pre-term birth and low birthweight were more likely to occur when OCs were discontinued 0-3 months pre-pregnancy, when using OCs containing <30 µg oestrogen and when using third-generation OCs. Associations with SGA were observed for OCs containing <30 µg oestrogen and for third- or fourth-generation OCs. Periconceptional OC use, particularly those containing oestrogen, was associated with increased risks of pre-eclampsia, pre-term birth, low birthweight and SGA.

Maternal cyclobenzaprine exposure and risk of birth defects in the National Birth Defects Prevention Study (1997-2011) and Birth Defects Study to Evaluate Pregnancy exposureS (2014-2018).

Cyclobenzaprine is a muscle relaxant indicated for acute pain. Little is known about cyclobenzaprine's safety during pregnancy. We explored the association between maternal cyclobenzaprine exposure and risk of birth defects among offspring. We combined data from two large, multi-site, population-based case-control studies in the United States. Cases were identified from birth defects registries across 10 states; controls were liveborn infants without birth defects randomly selected from the same catchment areas. Participants reported cyclobenzaprine use during the month before conception through the third month of pregnancy ("periconception") via computer-assisted telephone interview. We used logistic regression to assess associations between periconceptional cyclobenzaprine exposure and selected structural birth defects. We calculated crude odds ratios (OR) with corresponding 95% confidence intervals (CI). Our study included 33 615 cases and 13 110 controls. Overall, 51 case (0.15%) and 9 control (0.07%) participants reported periconceptional cyclobenzaprine use. We observed increased risk for all seven defects with ≥3 exposed cases: cleft palate (OR = 4.79, 95% CI 1.71-13.44), cleft lip (OR = 2.50, 95% CI 0.89-7.02), anorectal atresia/stenosis (OR = 6.91, 95% CI 1.67, 28.65), d-transposition of the great arteries (OR = 6.97, 95% CI 2.17-22.36), coarctation of the aorta (OR = 5.58, 95% CI 1.88-16.58), pulmonary valve stenosis (OR = 4.55, 95% CI 1.10-18.87), and secundum atrial septal defect (OR = 3.08, 95% CI 0.83-11.45). Even in our large sample, cyclobenzaprine use was rare. Our estimates are unadjusted and imprecise so should be interpreted cautiously. These hypothesis-generating results warrant confirmation and further research to explore possible mechanisms.

Risk of spontaneous abortion after periconceptional medication use: Time to tackle the methodological challenges.

Risk of spontaneous abortion after periconceptional medication use: Time to tackle the methodological challenges.

Periconceptional Folic Acid Use and Its Effects on Neural Tube Defects - Five Counties, Shanxi Province, China, 2010-2016.

Robust evidence indicates that supplementing with folic acid periconceptionally may decrease the risk of neural tube defects (NTDs) in fetuses. Over half of the mothers in both the NTD case group and the control group utilized folic acid supplements during the periconceptional period, showing no notable variations between the two groups. However, there was a significantly higher percentage of mothers with NTD cases who exhibited poor compliance in folic acid use compared to control mothers. A significantly lowered compliance with folic acid intake was observed among women facing unintended pregnancies and those with lower education levels. Universal education regarding folic acid action for women of childbearing age should be strengthened to improve compliance with folic acid supplementation in the periconceptional period and further reduce the prevalence of NTDs.

Periconceptional antibiotic use and spontaneous abortion: A prospective cohort study.

Many reproductive-aged North Americans use antibiotics in the weeks preceding conception or during early pregnancy. Antibiotic use may influence risk of spontaneous abortion (SAB) by disrupting the reproductive tract microbiome or treating harmful infections. However, this association has not been extensively studied. To determine the extent to which periconceptional antibiotic use is associated with the risk of SAB. We analysed data from an internet-based preconception cohort study of pregnancy planners. Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during 12 months of follow-up (n=7890). Participants completed an enrolment questionnaire during June 2013-September 2021 and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. Pregnant participants completed questionnaires in early (~8-9 weeks) and late (~32 weeks) gestation. We assessed antibiotic use, including type (penicillins, nitrofurantoin, cephalosporins and macrolides) and indication for use, during the previous 4 weeks on preconception questionnaires. Participants reported pregnancies and SAB on follow-up and pregnancy questionnaires. We used Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between periconceptional antibiotic use and SAB, controlling for potential demographic, medical, and lifestyle confounders. Nineteen percent (n=1537) of pregnancies ended in SAB. Participants reported periconceptional antibiotic use in 8% of pregnancies ending in SAB and 7% not ending in SAB. Periconceptional antibiotic use was not appreciably associated with SAB (adjusted HR 1.06, 95% CI 0.88, 1.28). We observed no strong associations between antibiotic type, indication for use, or recency of exposure and SAB risk. Periconceptional antibiotic use was not appreciably associated with SAB in this study. This association is likely complicated by antibiotic type and dosage, timing of conception, and the individual's overall health.

The effect of nicotine-containing products and fetal sex on placenta-associated circulating midpregnancy biomarkers

BackgroundIn utero exposure to nicotine, largely assessed by smoking, is a risk factor for impaired offspring health, while potential effects of non-combustible nicotine use such as snus (oral moist tobacco), are less well-known. Maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) may be viewed as “placenta health markers”, known to differ by fetal sex. Maternal smoking during pregnancy has been associated with lower levels of circulating sFlt-1, while the effect of snus on placenta-associated angiogenic factors is unknown. Our aim was to explore if snus and/or smoking exposure was associated with midpregnancy maternal levels of sFlt-1, PlGF and sFlt-1/PlGF ratio if these associations were modified by fetal sex.MethodsMidpregnancy (16–22 gestational weeks) serum from 2603 Scandinavian women enrolled in the population-based multi-center PreventADALL (Preventing Atopic Dermatitis and ALLergies in children) study was analysed for sFlt-1 and PlGF concentrations by electrochemiluminescence, deriving the sFlt-1/PGF ratio. Nicotine use was assessed by electronic questionnaires at enrollment in 2278 of the women. Univariable and multivariable linear regression models on log transformed outcomes were used to assess the association between nicotine use and biomarker levels. Interaction terms were included to identify whether the associations were modified by fetal sex.ResultsMedian sFlt-1, PlGF and sFlt-1/PlGF ratios among women with nicotine exposure information were similar to those of all included women and differed by fetal sex. Current snus use was significantly associated with reduced maternal circulating PlGF levels in adjusted analyses [β − 0.12, (95% CI − 0.20; 0.00) compared to never use, p = 0.020]. A significant interaction between fetal sex and snus exposure was observed for PIGF (p = 0.031). Prior or periconceptional snus use was significantly associated with PIGF in male fetus pregnancies [β − 0.05 (95% CI − 0.09 to (− 0.02)) and β − 0.07 (95% CI − 0.12 to (− 0.02)) compared to never use, p = 0.002]. Smoking was not significantly associated with any circulating biomarkers levels.ConclusionsMidpregnancy maternal angiogenic profile differed by periconceptional snus use and fetal sex. Snus exposure, perceived as “safe” by users, before or during pregnancy seems to affect midpregnancy placental health in a sex dimorphic manner.

Folate, Vitamin B12, and Homocysteine Levels in Women With Neural Tube Defect-Affected Pregnancy in Addis Ababa, Ethiopia.

BackgroundNeural tube defects (NTDs) are prevalent congenital defects associated with pre-pregnancy diet with low levels of maternal folate. They are linked to severe morbidity, disability, and mortality, as well as psychological and economic burdens.ObjectiveThe goal of this study was to determine the levels of folate, vitamin B12, and homocysteine in the blood of women who had a pregnancy impacted by NTDs.Subjects and MethodsA hospital-based case–control study was undertaken between September 2019 and August 2020. The study comprised a total of 100 cases and 167 controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of folate, vitamin B12, and homocysteine in the serum.ResultsOnly 39% of the cases and 54.5% of control mothers reported periconceptional use of folic acid/multivitamin, which indicated a statistically significant difference (p = 0.014). Logistic regression indicated that periconceptional use of folic acid/multivitamin was associated with NTDs (p = 0.015, OR = 1.873, 95% CI: 1.131–3.101). We found that 57% of the cases and 33.5% of controls, as well as 43% of cases and 20.4% of controls had serum folate and vitamin B12 levels below the cut-off value, respectively. Twenty-seven percent of the cases and 6.6% of controls had hyperhomocysteinemia (HHcy). The median concentrations of folate, vitamin B12, and homocysteine in cases and controls were 4.78 and 8.86 ng/ml; 266.23 and 455 pg/ml; 13.43 and 9.7 μmol/l, respectively. The median concentration of folate (p < 0.001) and vitamin B12 (p < 0.001) were significantly lower in the cases than controls, while the homocysteine concentration (p < 0.001) was significantly lower in the controls than cases. Folate [OR (95% CI) = 1.652 (1.226–2.225; p = 0.001)], vitamin B12 [OR (95% CI) = 1.890 (1.393–2.565; p < 0.001], and homocysteine [OR (95% CI) = 0.191 (0.09–0.405; p < 0.001)] levels were associated with NTDs.ConclusionFolate and vitamin B12 are deficient in both cases and control mothers. The lower levels of folate and vitamin B12 with an elevated homocysteine level in NTD-affected pregnancy may be an indication that these biochemical variables were risk factors for NTDs. Folate/multivitamin supplementation and/or food fortification should be promoted.

Periconceptional use of vitamin A and the risk of giving birth to a child with nonsyndromic orofacial clefts-A meta-analysis.

BackgroundWe conducted a meta‐analysis of observational epidemiological studies to evaluate the association between periconceptional use of vitamin A and the risk of giving birth to a child with nonsyndromic orofacial clefts (NSOFCs).MethodsWe carried out a systematic literature search of Embase, PubMed, Web of Science, Google Scholar, and OpenGrey from inception to June 30, 2021. Two reviewers independently evaluated the studies that met the inclusion criteria and filled out an abstraction form for each study. Study quality was assessed using the Newcastle‐Ottawa Assessment Scale (NOS). Adjusted estimates were pooled with an inverse variance weighting using a random‐effects model. Heterogeneity and publication bias were assessed using the Cochran's Q test and funnel plot, respectively.ResultsA total of six case–control studies with moderate risk of bias were included. The pooled OR showed a 20% reduction in the risk of NSOFCs for periconceptional use of vitamin A which was not statistically significant (OR = .80; 95% CI .54–1.17, p = .25). For nonsyndromic cleft lip with or without cleft palate (NSCL/P), the studies were homogenous, and the pooled estimate showed a 13% risk reduction, which was significant (OR = .87; 95% CI .77–.99, p = .03). For nonsyndromic cleft palate only (NSCPO), the pooled estimate showed a 33% lower likelihood, which was not statistically significant (OR = .67; 95% CI .42–1.08, p = .10).ConclusionOur results suggest a possible protective effect for the periconceptional use of vitamin A on the risk of NSCL/P. This finding should be investigated further in prospective studies across multiple populations.

Prevalence of neural tube defects at Debre Berhan Referral Hospital, North Shewa, Ethiopia. A hospital based retrospective cross-section study.

BackgroundNeural tube defect (NTD) is a structural defect of the central nervous system of the developing embryo during the first month of developmental process. Most congenital malformations are potentially preventable cause of perinatal morbidity and mortality. Worldwide, around 10% of infant mortalities are due to nervous system defects. In Ethiopia there are limited published data regarding the prevalence and established preventive strategy of NTDs. The purpose of this study was to assess the prevalence of NTDs among pregnancy outcomes in Debre Berhan Referral Hospital (DBRH), Ethiopia.MethodsHospital based retrospective cross sectional, descriptive study was conducted on registration of all pregnancy outcomes from August 30, 2017 to August 30, 2019 at DBRH, Ethiopia. The collected data were checked for completeness and consistencies, and cleaned, coded and entered using Epi data version 4.2 and exported to Statistical Package for Social Sciences (SPSS) software version 20 for analysis. Variables were interpreted per 1000 pregnancies and those variables having p<0.05 was considered as statistically significant.ResultsThe total prevalence of NTDs was 10.9 (95% CI 8.9 to 13.3) per 1000 pregnancies and the prevalence of each NTD type was anencephaly 5.6 (95% CI 4.2 to 7.4) per 1000 pregnancies, spina bifida 3.5 (95% CI 2.4 to 4.9) per 1000 pregnancies, encephalocele 1.1 (95% CI 0.6 to 2.0) per 1000 pregnancies, and both spina bifida and anencephaly 0.7(95% CI 0.3 to 1.4) per 1000 pregnancies. Among livebirths, aborted, stillbirths and medically terminated pregnancies (n = 8862), there were 50 anencephaly cases, 31 spina bifida cases, 10 encephalocele cases, and 6 cases affected by both spina bifida and anencephaly.ConclusionThe prevalence of NTDs in this study was among the highest globally reported. The total prevalence was 10.9 per 1000 pregnancies. Increased periconceptional folic acid use, counseling for women with certain medical illnesses at higher risk for NTDs, and early maternal screening for genetic factors are possible approaches to reduce in NTDs in the population.

Periconceptional folic acid use prevents both rare and common neural tube defects in China.

Neural tube defects (NTDs) encompass a variety of distinct types. We assessed if the preventive effect of folic acid (FA) varied by NTD type and infant sex. We examined all pregnancies with NTD status confirmation from a pregnancy-monitoring system in selected locations in northern and southern regions of China between 1993 and 1996. Women who took 400 μg of FA daily during 42 days after last menstrual period were considered FA users. We analyzed NTD prevalence by FA use status, NTD type, geographic region, and infant sex. Among 626,042 pregnancies, 700 were affected by an NTD. Among FA nonusers, 65 pregnancies (8.8 per 10,000) in the north and 51 pregnancies (1.2 per 10,000) in the south were affected by one of the two rare NTDs, that is, craniorachischisis, iniencephaly. FA use prevented occurrence of these two rare NTDs and reduced the prevalence of spina bifida (SB) by 78% (from 17.9 to 3.9 per 10,000) in the north and 51% (from 2.4 to 1.2 per 10,000) in the south. Among FA users, SB prevalence, including SB with high lesion level, was significantly reduced in both geographic regions. FA use reduced prevalence of anencephaly and encephalocele by 85% and 50%, respectively in the north, while it did not reduce the prevalence of these two NTDs in the south. There was a greater reduction in NTD prevalence in female than in male infants and fetuses. This is the first study to show that FA prevents the entire spectrum of NTD types.

Periconceptional and antenatal nutritional supplement use in Irish women: data from the improved study

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