Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study.

BACKGROUND & AIMS: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. METHODS: Data come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. RESULTS: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P = 0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. CONCLUSIONS: Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

The female upper reproductive tract harbors endogenous microbial profiles.

Introduction: The female reproductive tract harbours unique microbial communities (known as microbiota) which have been associated with reproductive functions in health and disease. While endometrial microbiome studies have shown that the uterus possesses higher bacterial diversity and richness compared to the vagina, the knowledge regarding the composition of the Fallopian tubes (FT) is lacking, especially in fertile women without any underlying conditions. Methods: To address this gap, our study included 19 patients who underwent abdominal hysterectomy for benign uterine pathology, and 5 women who underwent tubal ligation as a permanent contraceptive method at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). We analyzed the microbiome of samples collected from the FT and endometrium using 16S rRNA gene sequencing. Results: Our findings revealed distinct microbiome profiles in the endometrial and FT samples, indicating that the upper reproductive tract harbors an endogenous microbiome. However, these two sites also shared some similarities, with 69% of the detected taxa Being common to both. Interestingly, we identified seventeen bacterial taxa exclusively present in the FT samples, including the genera Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes, and Paracoccus, among others. On the other hand, 10 bacterial taxa were only found in the endometrium, including the genera Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Furthermore, our study highlighted the influence of the endometrial collection method on the findings. Samples obtained transcervically showed a dominance of the genus Lactobacillus, which may indicate potential vaginal contamination. In contrast, uterine samples obtained through hysterescopy revealed higher abundance of the genera Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus, and Streptococcus. Discussion: Although the upper reproductive tract appears to have a low microbial biomass, our results suggest that the endometrial and FT microbiome is unique to each individual. In fact, samples obtained from the same individual showed more microbial similarity between the endometrium and FT compared to samples from different women. Understanding the composition of the female upper reproductive microbiome provides valuable insights into the natural microenvironment where processes such as oocyte fertilization, embryo development and implantation occur. This knowledge can improve in vitro fertilization and embryo culture conditions for the treatment of infertility.

Prediction of the mode of delivery using artificial intelligence algorithms.

BACKGROUND AND OBJECTIVE: Mode of delivery is one of the issues that most concerns obstetricians. The caesarean section rate has increased progressively in recent years, exceeding the limit recommended by health institutions. Obstetricians generally lack the necessary technology to help them decide whether a caesarean delivery is appropriate based on antepartum and intrapartum conditions. METHODS: In this study, we have tested the suitability of using three popular artificial intelligence algorithms, Support Vector Machines, Multilayer Perceptron and, Random Forest, to develop a clinical decision support system for the prediction of the mode of delivery according to three categories: caesarean section, euthocic vaginal delivery and, instrumental vaginal delivery. For this purpose, we used a comprehensive clinical database consisting of 25,038 records with 48 attributes of women who attended to give birth at the Service of Obstetrics and Gynaecology of the University Clinical Hospital "Virgen de la Arrixaca" in the Murcia Region (Spain) from January of 2016 to January 2019. Women involved were patients with singleton pregnancies who attended to the emergency room on active labour or undergoing a planned induction of labour for medical reasons. RESULTS: The three implemented algorithms showed a similar performance, all of them reaching an accuracy equal to or above 90% in the classification between caesarean and vaginal deliveries and somewhat lower, around 87% between instrumental and euthocic. CONCLUSIONS: The results validate the use of these algorithms to build a clinical decision system to help gynaecologists to predict the mode of delivery.

Physicochemical and Functional Characterization of Female Reproductive Fluids: A Report of the First Two Infants Born Following Addition of Their Mother's Fluids to the Embryo Culture Media.

Culture media supplemented with reproductive fluids (RF) have been used in livestock species, improving the efficiency and quality of in vitro produced embryos. However, usefulness in humans is still unknown. In this study, we collected human reproductive fluids (HRFs) ex vivo (from 25 patients undergoing abdominal hysterectomy plus bilateral salpingectomy) and in vivo (from 31 oocyte donors). Afterward, protocols to evaluate their osmolality, pH, total protein concentration, endotoxin level, and sterility were optimized, establishing security ranges for their use as natural additives. In addition, a functional assay was developed with bovine embryos grown in vitro in a medium supplemented with 1% of collected HRFs. Finally, a proof of concept was performed with six patients on post ovulation day 2 to evaluate the full-term viability of embryos grown in media supplemented with autologous uterine fluid, collected under in vivo conditions. Two of the embryos resulted in successful pregnancy and delivery of healthy babies. In conclusion, this study establishes a complete quality control sheet of HRFs as additives for embryo culture media and shows first preliminary data on obtaining healthy offspring derived from embryos grown in media supplemented with HRFs.

Health-Related Quality of Life in Adult Spanish Women with Endometriomas or Deep Infiltrating Endometriosis: A Case-Control Study.

Endometriosis is a disabling disease that may significantly compromise a woman's social relationships, sexuality, and mental health. Considering the impact of endometriomas and deep infiltrating endometriosis (DIE) on quality of life and the limited number of papers on this topic, the objective of this study was to assess health-related quality of life (HRQoL) in adult Spanish women with the condition. A case-control study was conducted on a group of 99 patients with ovarian endometriomas or DIE and 157 controls. Women underwent physical and gynecological examinations, and they completed health questionnaires including the Short Form-12v2 (SF-12v2), a survey for HRQoL. Eight scales and two component summary scores (Physical (PCS) and Mental (MCS), respectively) were calculated. Women with endometriomas or DIE had significantly worse PCS: 47.7 ± 9.7 vs. 56.1 ± 5.9, respectively (p < 0.001) compared to controls, as well as lower scores on seven out of the eight scales (p < 0.01). No significant differences were found for the MCS. Conclusions: HRQoL was significantly lower in patients with endometriomas or DIE compared to controls. If confirmed, these results may have important implications for prevention, clinical practice, and intervention.

Are Dietary Indices Associated with Polycystic Ovary Syndrome and Its Phenotypes? A Preliminary Study.

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder which impairs ovarian function. The adherence to healthy dietary patterns and physical exercise are the first line of recommended treatment for PCOS patients, but it is yet unclear what type of diet is more adequate. In this case-control study, we explored associations between adherence to five dietary quality indices and the presence of PCOS. We enrolled 126 cases of PCOS and 159 controls living in Murcia (Spain). Diagnostic of PCOS and its phenotypes were established following the Rotterdam criteria (hyperandrogenism (H), oligoanovulation (O), polycystic ovaries morphology (POM)). We used a validated food frequency questionnaires to calculate the scores of five dietary indices: alternate Healthy Eating index (AHEI), AHEI-2010, relative Mediterranean Dietary Score (rMED), alternate Mediterranean Dietary Score (aMED) and Dietary Approaches to Stop Hypertension (DASH). We used multivariable logistic regression to estimate adjusted odds ratios and confidence intervals. In the multivariable analysis, AHEI-2010 index was inversely associated with Hyperandrogenism + Oligoanovulation PCOS phenotype (ORQ3 vs. Q1 = 0.1; 95% CI: (0.0; 0.9); Pfor trend = 0.02). We did not find any statistical significant association between dietary indices and total anovulatory or ovulatory PCOS. However, further studies with higher sample sizes exploring these associations among the diverse phenotypes of PCOS are highly warranted.

Is dispositional optimism associated with endometriomas and deep infiltrating endometriosis?

INTRODUCTION: Endometriosis is a chronic painful condition characterized by high prognostic uncertainty, as well as the threat of infertility and emotional symptoms that may affect many aspects of women, including psychological characteristics like dispositional optimism. Considering the impact of endometriosis on psychological health and the paucity of papers on this topic, the aim of this study is to explore optimism and associated factors in endometriosis. METHODS: A case-control study was performed on a group of 95 women with endometriosis and 156 controls. All participants completed the Life Orientation Test-Revised (LOT-R), a self-administered tool for assessing dispositional optimism. Pain severity, medication, gynecological and socio-demographic information was also collected. RESULTS: Low optimism was observed for women with endometriosis compared to controls even after covariate adjustment (LOT-R global scores: 14.5 vs. 15.9 points, p = .045). CONCLUSIONS: This study provides the first evidence that a personality dimension with many prognostic implications may be altered in women with endometriosis. Our findings highlight the importance of a broader understanding of this condition, treating this disorder from a biopsychosocial perspective and suggests the need for non-medical attention within a multidisciplinary team.

Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.

Short Femur in the Second Trimester Scan Is Related to Maternal Preeclampsia and Small for Gestational Age Newborns.

OBJECTIVE: To determine the contribution of short femur diaphysis length (FDL) at 19-22 weeks of gestation in the prediction of adverse pregnancy outcomes. METHODS: The study included singleton pregnant women who underwent a routine anomaly scan at 19-22 weeks of gestation at the Virgen de la Arrixaca University Clinical Hospital (Murcia, Spain) between August 2011 and August 2012. Fetal biometry and Doppler ultrasound of uterine arteries were assessed as part of the anomaly scan, and the mean pulsatility index of both uterine arteries was recorded. Maternal obstetric characteristics, such as ethnicity, age, weight, parity, cigarette smoking, and medical history including hypertension and diabetes mellitus were collected from our database system. RESULTS: A total of 6,366 women were included in the study after excluding cases with abnormal karyotype, major fetal abnormalities, or termination of pregnancy. There were 88 cases of preeclampsia (PE) (1.4%). Logistic regression was performed including maternal and fetal characteristics. Short FDL at 19-22 weeks was significantly associated with subsequent development of PE (OR = 0.89, 95% CI: 0.80-0.99, p = 0.025). The best model to predict PE from our sample included gestational age at scan, parity, maternal weight, chronic hypertension, mean pulsatility index in the uterine arteries, and FDL (AUC = 0.78, 95% CI: 0.71-0.84). Regarding small for gestational age (SGA) neonates, there were also significant differences in FDL and FDL <5th centile between the control group and SGA newborns below the 3rd, 5th, and 10th centile. In the groups of preterm births (delivery before 32, 34, and 37 weeks), there were no differences in FDL compared with the control group (term births). DISCUSSION: Our results suggest that FDL at 19-22 weeks of gestation is an independent predictor of PE and SGA newborns.

Which Low-Abundance Proteins are Present in the Human Milieu of Gamete/Embryo Maternal Interaction?

The improvement of the embryo culture media is of high relevance due to its influence on successful implantation rates, pregnancy, neonatal outcomes, and potential effects in adult life. The ideal conditions for embryo development are those naturally occurring in the female reproductive tract, i.e., the oviductal and uterine fluids. To shed light on the differences between chemical and natural media, we performed the first comparative study of the low abundance proteins in plasma, uterine, and oviductal fluid collected, simultaneously, from healthy and fertile women that underwent a salpingectomy. The rationale for this design derives from the fact that high-abundant proteins in these fluids are usually those coming from blood serum and frequently mask the detection of low abundant proteins with a potentially significant role in specific processes related to the embryo-maternal interaction. The proteomic analysis by 1D-nano LC ESI-MSMS detected several proteins in higher amounts in oviductal fluid when compared to uterine and plasma samples (RL3, GSTA1, EZRI, DPYSL3, GARS, HSP90A). Such oviductal fluid proteins could be a target to improve fertilization rates and early embryo development if used in the culture media. In conclusion, this study presents a high-throughput analysis of female reproductive tract fluids and contributes to the knowledge of oviductal and uterine secretome.

A decision support system for predicting the treatment of ectopic pregnancies.

BACKGROUND AND OBJECTIVE: Ectopic pregnancy is an important cause of morbidity and mortality worldwide. An early diagnosis, as well as the choice of the most suitable treatment for the patient is crucial to avoid possible complications. According to different factors an ectopic pregnancy must be treated from surgery, using a pharmacological treatment or following a conservative treatment. In this paper, a clinical decision support systems based on artificial intelligence algorithms has been developed to help clinicians to choose the initial treatment to be followed by the patient. METHODS: A decision support system based on a three stages classifier has been developed. Each stage acts as a filter and allows re-evaluation of the classification made in the previous stage in order to find diagnostic errors. This classifier has been implemented and tested for four different aid algorithms: Multilayer Perceptron, Deep Learning, Support Vector Machine and Naives Bayes. RESULTS: The results prove that the evaluated algorithms Support Vector Machine and Multilayer Perceptron can be useful to help gynecologists in their decisions about initial treatment, especially with Support Vector Machine that presents accuracy, sensitivity and specificity outcomes about 96.1%, 96% and 98%, respectively. CONCLUSIONS: According to the results, it is feasible to develop a clinical decision support system using the algorithms that present a higher precision. This system would help gynecologists to take the most accurate decision about the initial treatment, thus avoiding future complications.

Anogenital Distance and Perineal Measurements of the Pelvic Organ Prolapse (POP) Quantification System.

Anogenital distance (AGD) is a sexually dimorphic attribute, twice longer in males than in females, and a marker of intrauterine hormonal environment. Interest in AGD measurements is increasing due to mounting evidence on their potential clinical implications. A parallel set of perineal measurements, the Pelvic Organ Prolapse Quantification System (POP-Q), include similar, but not exactly the same, landmarks: the perineal body (PB) and the genital hiatus (GH) lengths. However, clinical reproducibility of both perineal measurements and their usefulness to describe perineal anthropometry needs to be elucidated. To our knowledge, there is no publication in video format showing the methodology of these measurements. The main objective of this work is to show how to properly perform perineal anthropometry, including measurements of the AGD in its two variants [anoclitoral (AGDAC) and anofourchette (AGDAF)], genital hiatus (GH) and perineal body (PB). Moreover, we explored if there were differences in these measurements in women with and without Pelvic Organ Prolapse (POP). We research whether the anthropometric characteristics of the perineum, such as AGD (which is determined prenatally), may be altered in these women and be an independent etiological factor for pelvic floor dysfunction. We show two different ways of measuring perineal lengths, as they might be quite comparable. Our suggestion is that unifying perineal measurements could be useful for clinical and biomedical investigation. More studies are needed in order to compare GH and PB measurements and its AGD counterparts to analyze which procedures are more reproducible with less intra and interobserver variability.

Variations in clinical presentation of unicornuate uterus with non-communicating rudimentary horn (class IIB of the American Fertility Society classification).

OBJECTIVE: The unicornuate uterus is a rare uterine malformation (2.4-13.7% of all uterine malformations (Engmann et al., 2004)) which usually features a rudimentary accessory horn in more than 75% of the cases. Pregnancy in the rudimentary horn is rare, but the complications attached to such pregnancies could be defined as the first clinical manifestation of rudimentary horn. CASE REPORTS: We hereby describe five cases of unicornuate uterus with rudimentary horn (UUWRH), each one with a different clinical presentation and without any correct preoperative diagnosis, and henceforth reflect on the practical aspects learnt about the differential diagnosis and management of this rare malformation. CONCLUSION: Our experience with UUWRH is that perhaps asymptomatic cases are not as rare as reported in medical literature. We highlight the need for a greater awareness of the differential diagnosis of genital malformations and accurate in the exact subtype and their correct treatment.

External iliac artery Doppler assessment in the prediction of adverse pregnancy outcomes.

PURPOSE: The purpose of this study is to investigate the potential role of the mean external iliac artery pulsatility index (EIA-PI) as a predictor of adverse obstetric outcomes such as preeclampsia, gestational hypertension and small for gestational age (SGA). METHODS: In women attending for first trimester screening at 11 + 0-13 + 6 weeks of gestation, we recorded maternal characteristics and measured EIA mean PI and uterine artery mean PI. We compared EIA mean PI in those that developed preeclampsia (n = 84), gestational hypertension (n = 50) or small for gestational age (n = 444) with those unaffected (n = 3736). Regression analysis was used to first determine which of the factors among the maternal variables were significant predictors of EIA mean PI in the unaffected group and, second, to predict adverse pregnancy outcomes. RESULTS: In the unaffected group, EIA mean PI increased with maternal age and decreased with mean blood pressure. Additionally, EIA mean PI was lower in cigarette smokers. Compared with the unaffected group, EIA mean PI was significantly lower in women who develop gestational hypertension or SGA below third centile. CONCLUSION: EIA mean PI in the first trimester is decreased in women who develop gestational hypertension and in those complicated by SGA below third centile. More studies are needed to confirm these findings.

Insulin Treatment May Alter Fatty Acid Carriers in Placentas from Gestational Diabetes Subjects.

There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM.

Central pontine myelinolysis during pregnancy: Pathogenesis, diagnosis and management.

Central pontine myelinolysis (CPM) is a rare condition usually caused by rapid sodium correction in hyponatraemia after a severe neurological syndrome. Only few cases have been reported during pregnancy, most of which were reported in patients with hyperemesis. We describe the successful management of the first case of twin pregnancy in a patient who presented with CPM after treatment for premature labour and then review the literature on CPM in pregnancy (aetiology, diagnosis and management). Our patient required emergency delivery to achieve electrolyte and fluid balance. At six months, the twins remained asymptomatic and the mother had minor sequelae. The aetiology is not clear, and there is no evidence regarding the optimal treatment or prognosis of CPM. In our patient, desmopressin-contaminated atosiban showed a certain probability in the Karch-Lasagne algorithm of a causality relationship between hyponatraemia and the drug. To our knowledge, this is the first case of myelinolysis reported in a twin pregnancy possibly related to desmopressin-contaminated atosiban.

Uterine and umbilical artery Doppler at 28 weeks for predicting adverse pregnancy outcomes in women with abnormal uterine artery Doppler findings in the early second trimester.

OBJECTIVE: The objective of this study was to determine the contribution of uterine (UtA) and umbilical arteries (UA) Doppler examination at 28 weeks to predict adverse pregnancy outcomes in women who had increased resistance in UtA in the early second trimester. METHODS: Women with UtA mean pulsatility index (PI) above the 95th centile at 19-22 weeks of gestation were offered a growth scan including Doppler examination of UtA and UA at 28 weeks. Adverse pregnancy outcomes included small for gestational age (SGA), defined as birth weight below the tenth centile, preeclampsia (PE) and early-onset PE (PE before 34 weeks). RESULTS: We studied 266 pregnant women with elevated PI in the UtAs in the second trimester and ultrasound reassessment at 28 weeks. UtA PI >95th centile at 28 weeks was associated with subsequent PE [odds ratio (OR): 10.0, 95% CI: 2.3-43.5], early-onset PE (OR: 57.7, 95% CI: 3.8-87.6) and SGA less than the tenth centile (OR: 5.5, 2.2-13.9). UA PI >95th centile at 28 weeks was not significantly associated with any adverse outcome. CONCLUSIONS: In women with abnormal UtA Doppler in the early second trimester scan, persistence of elevated UtA PI, but not abnormal UA PI, is associated with adverse pregnancy outcomes including PE, early-onset PE and SGA. © 2014 John Wiley & Sons, Ltd.

Omega 3 fatty acids, gestation and pregnancy outcomes.

Pregnancy is associated with a reduction in maternal serum docosahexaenoic acid (DHA, 22:6 n-3) percentage and its possible depletion in the maternal store. Since the synthesis of long chain polyunsaturated fatty acids (LCPUFA) in the fetus and placenta is low, both the maternal LCPUFA status and placental function are critical for their supply to the fetus. Maternal supplementation with DHA up to 1 g/d or 2·7 g n-3 LCPUFA did not have any harmful effect. DHA supplementation in large studies slightly the enhanced length of gestation (by about 2 days), which may increase the birth weight by about 50 g at delivery. However no advice can be given on their general using to avoid preterm deliveries in low or high risk pregnancies. Several studies, but not all, reported improvements of the offspring in some neurodevelopmental tests as a result of DHA supplementation during gestation, or, at least, positive relationships between maternal or cord serum DHA percentages and cognitive skills in young children. The effect seems more evident in children with low DHA proportions, which raises the question of how to identify those mothers who might have a poor DHA status and who could benefit from such supplementation. Most studies on the effects of n-3 LCPUFA supplementation during pregnancy on maternal depression were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. In contrast, the effects of n-3 LCPUFA supplementation on reducing allergic diseases in offspring are promising.