Familial Beckwith-Wiedemann syndrome: Prenatal manifestation and a possible expansion of the phenotype.

We describe a case of Beckwith-Wiedemann syndrome (BWS) demonstrating pre- and post-natal intra-familial variability. Our first encounter with the family occurred in the 1990s following the birth of 3 affected offspring. The first two pregnancies presented with exomphalos and elevated second trimester maternal serum alpha-fetoprotein (msAFP, 3.43 and 4.01 MOM, respectively) as well as elevated maternal human chorionic gonadotrophin (mhCG, 4.33 and 8.8 MOM, respectively). The diagnosis of BWS was confirmed postnatally in both cases. The third ongoing pregnancy presented only with elevated mhCG (7.09 MOM) and no malformation. Nonetheless BWS was suspected. The diagnosis was confirmed postnatally with clinical manifestations including macroglossia and cleft palate. Two affected female siblings were also diagnosed with Mullerian agenesis in adulthood. Suspecting a common genetic etiology, sequencing of the CDKN1C gene revealed a maternally inherited, likely pathogenic variant (NM_000076.2: c.367_385del; p.(Ala123Serfs*143)) causative of BWS. Chromosomal microarray and whole exome sequencing did not reveal any other pathogenic variant that would explain the Mullerian agenesis. One of the affected females underwent successful preimplantation genetic testing (PGT) with a surrogate and gave birth to a healthy female. To the best of our knowledge, this is the first report of Mullerian agenesis as a possible rare expansion of the BWS phenotype. In addition, this case highlights the potential role of abnormal second trimester biochemical markers (msAFP, mHCG) as possible indicators of BWS, especially in familial cases.

Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1-related syndrome.

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra-renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one-day-old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post-zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow-up studies for presumed de novo and low-level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.

Absence of Evidence of Zika Virus Infection in Cord Blood and Urine from Newborns with Congenital Abnormalities, Indonesia.

Zika virus (ZIKV) has recently been confirmed as endemic in Indonesia, but no congenital anomalies (CA) related to ZIKV infection have been reported. We performed molecular and serological testing for ZIKV and other flaviviruses on cord serum and urine samples collected in October 2016 to April 2017 during a prospective, cross-sectional study of neonates in Jakarta, Indonesia. Of a total of 429 neonates, 53 had CA, including 14 with microcephaly. These 53, and 113 neonate controls without evidence of CA, were tested by ZIKV-specific real-time reverse transcription polymerase chain reaction (RT-PCR), pan-flavivirus RT-PCR, anti-ZIKV and anti-DENV IgM ELISA, and plaque reduction neutralization test. There was no evidence of ZIKV infection among neonates in either the CA or non-CA cohorts, except in three cases with low titers of anti-ZIKV neutralizing antibodies. Further routine evaluation throughout Indonesia of pregnant women and their newborns for exposure to ZIKV should be a high priority for determining risk.

Type 2 Diabetes in Pregnancy.

Hyperglycemia is common during pregnancy, involving multisystem adaptations. Pregnancy-induced metabolic changes increase insulin resistance. Pregnancy-induced insulin resistance adds to preexisting insulin resistance. Preexisting pancreatic ß-cell defect compromises the ability to enhance insulin secretion, leading to hyperglycemia. Women with type 2 DM have similar rates of major congenital malformations, stillbirth, and neonatal mortality, but an even higher risk of perinatal mortality. In utero type 2 DM exposure confers greater risk and reduces time to development of type 2 DM in offspring. Preconception care to improve metabolic control in women with type 2 diabetes is critical.

Low prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser syndrome.

STUDY QUESTION: Is there an increased prevalence of male microchimerism in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, as evidence of fetal exposure to blood and anti-Müllerian hormone (AMH) from a (vanished) male co-twin resulting in regression of the Müllerian duct derivatives? SUMMARY ANSWER: Predominant absence of male microchimerism in adult women with MRKH syndrome does not support our hypothesis that intrauterine blood exchange with a (vanished) male co-twin is the pathophysiological mechanism. WHAT IS KNOWN ALREADY: The etiology of MRKH is unclear. Research on the phenotype analogous condition in cattle (freemartinism) has yielded the hypothesis that Müllerian duct development is inhibited by exposure to AMH in utero. In cattle, the male co-twin has been identified as the source for AMH, which is transferred via placental blood exchange. In human twins, a similar exchange of cellular material has been documented by detection of chimerism, but it is unknown whether this has clinical consequences. STUDY DESIGN, SIZE, DURATION: An observational case-control study was performed to compare the presence of male microchimerism in women with MRKH syndrome and control women. Through recruitment via the Dutch patients' association of women with MRKH (comprising 300 members who were informed by email or regular mail), we enrolled 96 patients between January 2017 and July 2017. The control group consisted of 100 women who reported never having been pregnant. PARTICIPANTS/MATERIALS, SETTING, METHODS: After written informed consent, peripheral blood samples were obtained by venipuncture, and genomic DNA was extracted. Male microchimerism was detected by Y-chromosome-specific real-time quantitative PCR, with use of DYS14 marker. Possible other sources for microchimerism, for example older brothers, were evaluated using questionnaire data. MAIN RESULTS AND THE ROLE OF CHANCE: The final analysis included 194 women: 95 women with MRKH syndrome with a mean age of 40.9 years and 99 control women with a mean age of 30.2 years. In total, 54 women (56.8%) were identified as having typical MRKH syndrome, and 41 women (43.2%) were identified as having atypical MRKH syndrome (when extra-genital malformations were present). The prevalence of male microchimerism was significantly higher in the control group than in the MRKH group (17.2% versus 5.3%, P = 0.009). After correcting for age, women in the control group were 5.8 times more likely to have male microchimerism (odds ratio 5.84 (CI 1.59-21.47), P = 0.008). The mean concentration of male microchimerism in the positive samples was 56.0 male genome equivalent per 1 000 000 cells. The prevalence of male microchimerism was similar in women with typical MRKH syndrome and atypical MRKH syndrome (5.6% versus 4.9%, P = 0.884). There were no differences between women with or without microchimerism in occurrence of alternative sources of XY cells, such as older brothers, previous blood transfusion, or history of sexual intercourse. LIMITATIONS, REASON FOR CAUTION: We are not able to draw definitive conclusions regarding the occurrence of AMH exchange during embryologic development in women with MRKH syndrome. Our subject population includes all adult women and therefore is reliant on long-term prevalence of microchimerism. Moreover, we have only tested blood, and, theoretically, the cells may have grafted anywhere in the body during development. It must also be considered that the exchange of AMH may occur without the transfusion of XY cells and therefore cannot be discovered by chimerism detection. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to test the theory that freemartinism causes the MRKH syndrome in humans. The study aimed to test the presence of male microchimerism in women with MRKH syndrome as a reflection of early fetal exposure to blood and AMH from a male (vanished) co-twin. We found that male microchimerism was only present in 5.3% of the women with MRKH syndrome, a significantly lower percentage than in the control group (17.2%). Our results do not provide evidence for an increased male microchimerism in adult women with MRKH as a product of intrauterine blood exchange. However, the significant difference in favor of the control group is of interest to the ongoing discussion on microchimeric cell transfer and the possible sources of XY cells. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Dutch trial register, NTR5961.

Association Between Extra-Genital Congenital Anomalies and Hypospadias Outcome.

Extra-genital congenital anomalies are often present in cases of hypospadias, but it is unclear whether they have an association with the outcome of hypospadias surgery. The aim of this study was to review all hypospadias cases that had surgery between 2009 and 2015 at a single centre and identify clinical determinants of the surgical outcome. An extra-genital congenital anomaly was reported in 139 (22%) boys and 62 (10%) had more than 1 anomaly. Of the 626 boys, 54 (9%), including 44 with proximal hypospadias, had endocrine as well as limited genetic evaluation. Of these, 10 (19%) had a biochemical evidence of hypogonadism and 5 (9%) had a molecular genetic abnormality. At least 1 complication was reported in 167 (27%) patients, with 20% of complications (most frequently fistula) occurring after 2 years of surgery. The severity of hypospadias and the existence of other anomalies were clinical factors that were independently associated with an increased risk of complications (p < 0.001). In conclusion, complications following surgery are more likely in those cases that are proximal or who have additional extra-genital anomalies. To understand the biological basis of these complications, there is a greater need to understand the aetiology of such cases.

Associations between the Level of Trace Elements and Minerals and Folate in Maternal Serum and Amniotic Fluid and Congenital Abnormalities.

Congenital birth defects may result in a critical condition affecting the baby, including severe fetal/neonatal handicap and mortality. Several studies have shown that genetic, nutritional, and environmental factors may have an impact on fetal development and neonatal health. The relevance of essential and toxic elements on fetal development has not yet been fully investigated, and the results of recent research indicate that these elements may be crucial in the assessment of the risk of malformations in neonates. We determined the association between essential and toxic elements and the level of folate in maternal serum (MS) and amniotic fluid (AF), along with neonatal abnormalities. A total of 258 pregnant Polish women in the age group of 17⁻42 years participated in this study. AF and MS were collected during vaginal delivery or during cesarean section. An inductively coupled plasma mass spectrometry technique was used to determine the levels of various elements in AF and MS. The results of this exploratory study indicate that the levels of essential and toxic elements are associated with fetal and newborn anatomical abnormalities and growth disorders.

The effect of intestinal flora on the neural development of severe hyperbilirubinemia neonates.

OBJECTIVE: To investigate the effect of intestinal flora on the neural development of severe hyperbilirubinemia neonates. PATIENTS AND METHODS: The clinical data of 108 severe hyperbilirubinemia neonates admitted to the Dezhou People's Hospital from January 2015 through January 2018 were analyzed, and all newborns had a serum total bilirubin level > 342 µmol/L. Based on whether they suffered from neural development abnormalities, the neonatal patients were divided into the neural abnormality group (n=52) and the non-neural abnormality group (n=56). The unconjugated bilirubin levels in serum and cerebrospinal fluid (CSF) and the composition of intestinal flora were compared. RESULTS: Among 108 neonates, there were 55 cases with developmental abnormalities, in which 52 (48.13%) cases had neural developmental abnormalities, mainly epileptic patients. The serum and CSF unconjugated bilirubin levels of the neonatal patients in the neural abnormality group were (466.25±97.64) µmol/L and (9.64±2.98) µmol/L, respectively, which were higher than those in neonatal patients of the non-neural abnormality group [(357.89±72.53) µmol/L and (6.73±3.11) µmol/L], with statistically significant differences (p<0.05). The abundance of intestinal flora genus in the neonates in the neural abnormality group was lower than that in the non-neural abnormality group, and the comparisons of Fusobacterium, Catabacter, Succinivibrio, Clostridium and Bacteroides between the two groups showed statistically significant differences (p<0.05). DISCUSSION: The intestinal micro-ecological environment of newborns was vulnerable and easily affected by many factors such as methods of delivery, feeding ways and eating habits of their mothers. This study investigated the effects of intestinal flora on the neural development of neonates with severe hyperbilirubinemia. The results showed that, due to decreased intestinal flora diversity, the serum and cerebrospinal fluid bilirubin levels were elevated, and the abnormal rate of neural development was increased. CONCLUSIONS: Severe hyperbilirubinemia neonates with neural abnormalities have decreased diversity of intestinal flora genus and relatively high serum and CSF bilirubin levels, probably because the decrease in the diversity of intestinal flora genus leads to the change of the blood-CSF barrier permeability, leading to raised levels of bilirubin in serum and CSF, thus affecting the neural development of neonatal patients.

Hyperandrogenemia and ovarian reserve in patients with Mayer-Rokitansky-Küster-Hauser syndrome type 1 and 2: potential influences on ovarian stimulation.

PURPOSE: This study aimed to analyze the hormone profiles, to detect the rate of hyperandrogenemia and to investigate the potential effect of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) on ovarian reserve, as reflected by the serum Anti-Mullerian hormone (AMH) levels. Clinical implications were analyzed by including our own experiences with three patients after ovarian stimulation in preparation for uterus transplantation. METHODS: Serum samples of 100 patients with MRKHS (50 patients with MRKHS type 1 and 50 with type 2) were analyzed and compared to 50 individually age-matched healthy controls. Blood samples for hormone analyses were collected routinely during the clinical visit. RESULTS: The mean age was 20.0 years for MRKHS type 1, MRKHS type 2 and healthy controls. Compared to healthy controls, there was no significant difference in AMH values in the MRKH patients. As shown in previous studies, the proportion of hyperandrogenemia without clinical symptoms was significantly higher in MRKHS type 1 (52%; p < 0.001) and type 2 (56%; p < 0.001) patients when compared to age-matched controls. In preparation for uterus transplantation, three patients were stimulated with FSH/hMG for mean 14.2 days and the mean number of aspirated oocytes was 13.2 (3-22), while 8.3 (2-10) oocytes could be fertilized and cryopreserved. The mean fertilization rate was 51.2% (30-67%). CONCLUSION: The rate of hyperandrogenemia was significantly higher in MRKH patients compared to healthy age-matched controls. Though, ovarian reserve (AMH level) was not reduced compared to controls. Future studies are needed to identify optimal ovarian stimulation protocols as well as to implement a systematic multicenter reporting system.

Selected trace elements concentrations in pregnancy and their possible role - literature review.

The aim of this study was to review the role of selected trace elements in pregnancy and fetal development. Citations related to the role of iron (Fe), zinc (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were searched in PubMed, Medline, Web of Science, using keywords and MeSH terms. Inadequate supply of trace elements can cause abnormalities of fetal development and predispose a child to disorders later on in life. Trace elements are the key elements of complex enzymes responsible for the modulation of the antioxidant defense system of the organism. It has been suggested that there is a correlation between reduced levels of trace elements essential for antioxidant function in the body of pregnant women, and an increased risk of developing preeclampsia. Trace elements are components of numerous regulatory enzymes and hormones essential to the division and differentiation of fetal cells and their further development. Mineral deficiencies in pregnant women can cause birth defects of the central nervous system, and growth disorders. Future research should be directed to explain the interaction between trace elements, and establish the optimum levels of macro and micronutrients supplementation, as well as determine the reference values for trace elements in the maternal serum, umbilical cord blood and amniotic fluid.

Does the serum uric acid level have any relation to arterial stiffness or blood pressure in adults with congenital renal agenesis and/or hypoplasia?

BACKGROUND: The relationship between serum uric acid and arterial stiffness or blood pressure is not clear. The serum uric acid level and its association with cardiovascular risk is not well known in patients with reduced renal mass. We aimed to investigate the relation between serum uric acid levels and arterial stiffness and also blood pressure in patients with congenital renal agenesis and/or hypoplasia. MATERIAL AND METHODS: In this single center, cross-sectional study, a total of 55 patients (39 (% 70.9) with unilateral small kidney and 16 (%29.1) with renal agenesis) were included. The median age was 35 (21-50) years. The study population was divided into tertiles of serum uric acid (according to 2.40-3.96, 3.97-5.10, and 5.11-9.80 mg/dl cut-off values of serum uric acid levels). Official and 24-h ambulatory non-invasive blood pressures of all patients were measured. The arterial stiffness was assessed by pulse wave velocity (PWV). RESULTS: PWV values were increased from first to third tertile (5.5 ± 0.6, 5.7 ± 0.8, 6.1 ± 0.7, respectively), but this gradual increase between tertiles did not reach significance. Linear regression analyses showed a positive correlation between serum uric acid levels and PWV (ß = 0.40, p = 0.010), but no correlation was found between uric acid and daytime systolic blood pressure (ß = 0.24, p = 0.345). CONCLUSION: In congenital renal agenesis/hypoplasia, the serum uric acid level was positively correlated with arterial stiffness, but there was no correlation with blood pressure.

INTRA-OPERATIVE NEED FOR GLUCOSE IN NEWBORNS.

INTRODUCTION: One ofthe important goals of intraoperativefluid therapy in neonates is to ensure normal glycemic status. However there is no definitive guidance on the issue of intraoperative administration solutions containing glucose. MATERIALS AND METHODS: a single-center study of intraoperative glycemic status in 60 newborns with congenital malformations was conducted. Age at the time of surgery amounted to Me 48 [24; 120] hours of life, the duration of surgery was 70 [60; 101] minutes. The children were divided into two groups: in group 1 (n = 30) intraoperative infusion therapy was only saline; in group 2 (n = 30) with salt solutions were simultaneously injected glucose in a dose of 2,3 mg/kg/ min. The glucose level in the blood was evaluated before operation, during operation every 30 minutes and at the end of surgical intervention, if it was necessary, was corrected. RESULTS: the study revealed high incidence of hypoglycemic conditions in children in group 1, especially during tracheal intubation and skin incision (40 episodes in 20 children). However the blood glucose level subsequently normalized and remained within the reference values. In group 2, the average glucose level in these stages was significantly greater than 4,4 [3,3; 5,2] mmol/l (p = 0,03), and did not go beyond normal values, remaining stable in all phases of the operation. There was a decrease in 2 times the frequency of episodes of hypoglycemia in group 2 (19 episodes in 12 patients). At the same time, more often fixed hyperglycemia in group 2. CONCLUSIONS: intraoperative blood glucose in newborns is unstable indicator and requires a precise dosing of glucose in the infusion to avoid Hypo- and hyperglycemia.

Phenotypic and clinical aspects of Mayer-Rokitansky-Küster-Hauser syndrome in a Chinese population: an analysis of 594 patients.

OBJECTIVE: To analyze the phenotypic and clinical aspects of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: Cross-sectional study. SETTING: University hospital. PATIENT(S): Five hundred and ninety-four patients with MRKH syndrome. INTERVENTION(S): Clinical examination, abdominal or perineal/rectal ultrasound, magnetic resonance imaging, hormonal profile, karyotype, and laparoscopy. MAIN OUTCOME MEASURE(S): Clinicopathologic data, VCUAM (vagina cervix uterus adnex-associated malformation) classification, types with cycle phase, and karyotype. RESULT(S): We identified associated malformations in 43 out of 594 (7.2%) cases of MRKH. The 594 patients could be grouped into hormone phases: 53.7% follicular, 35.2% luteal, and 11.1% ovulatory. The major karyotype of MRKH patients was 46,XX; abnormal karyotypes were found in two cases. CONCLUSION(S): A lower proportion of associated malformations were found when compared with those provided in the current literature. Renal anomalies were the most frequent associated malformations, and most of the patients presented with a normal karyotype. Given the large cohort of this study, the lower malformation rates might be related to geographic or referral patterns, so further investigation is warranted.

Comparison of markers of ovarian reserve between patients with complete müllerian agenesis and age-matched fertile and infertile controls.

OBJECTIVE: To investigate ovarian reserve in complete müllerian agenesis (CMA) patients and to compare the ovarian reserve of CMA patients with that of age-matched fertile and infertile controls. DESIGN: Prospective cohort study. SETTING: University gynecology outpatient clinic. PATIENT(S): Fifty-eight typical CMA (type A) patients, 8 atypical CMA (type B) patients, 39 fertile patients, and 38 infertile patients were compared for ovarian reserve. INTERVENTION(S): Ovarian reserve was evaluated via antimüllerian hormone (AMH) levels and antral follicle counts (AFCs). MAIN OUTCOME MEASURE(S): Investigation of ovarian reserve in CMA patients and a comparison of the ovarian reserve of the CMA patients with that of age-matched fertile and infertile controls. RESULT(S): Fifty-eight type A and eight type B CMA patients and 39 fertile and 38 infertile control patients were assessed for ovarian reserve. The mean (±SD) ages of the type A and type B CMA patients and the fertile and infertile groups were 25.8 ± 5.3, 33.3 ± 5.9, 32.6 ± 4.8, and 33.9 ± 3.3 years, respectively. After age standardization of the groups, AMH levels and AFCs were found to be lower in the atypical CMA group. The differences in AMH levels and AFC were found to be highly significant. CONCLUSION(S): The present study showed that atypical CMA patients had decreased ovarian reserve compared with age-matched fertile and infertile controls.

Deviant early pregnancy maternal triglyceride levels and increased risk of congenital anomalies: a prospective community-based cohort study.

OBJECTIVE: The maternal lipid profile could be of importance in congenital anomaly development. This study therefore investigates whether the maternal lipid profile during early pregnancy is associated with major nonsyndromic congenital anomalies (MNCA). DESIGN: Prospective community-based cohort study. SETTING: Amsterdam Born Children and their Development (ABCD) study. POPULATION: A cohort of 3074 pregnant women recruited in 2003-2004 and their offspring. METHODS: Non-fasting blood samples from pregnant women participating in the ABCD-study (median 12.9 weeks of gestation) were analysed for triglycerides (TG), cholesterol (TC), free fatty acids (FFA), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA) (n = 3074). The perinatal outcome (MNCA) was obtained from the Youth Health Care Registration and two questionnaires. Adjustment was made for ethnicity. MAIN OUTCOME MEASURE: MNCA prevalence. RESULTS: The prevalence of MNCA was 2.2% (n = 68: 20 cardiovascular, 25 bone and muscle, and 23 other single anomalies). A nonlinear association was found between maternal TG levels and MNCA prevalence. With a lower or higher level of maternal TG, the estimated probability increased: a TG level of 0.73 mmol/l (5th percentile), of 1.28 mmol/l (50th percentile), and of 2.35 mmol/l (95th percentile) corresponded with an estimated probability of 3.6, 2.1, and 2.9%, respectively. Unadjusted subgroup analyses showed that the U-shaped association was most prominent for cardiovascular congenital anomalies. Other lipids were not associated with MNCA. CONCLUSIONS: Both low and high maternal TG levels during early pregnancy were associated with an increased risk of MNCA in offspring. This suggests that an attempt should be made to normalise TG levels before or during early pregnancy; however, replication of our results is necessary before clinical practice recommendations can be made.

Bisphenol A and congenital developmental defects in humans.

Over 50% of the causes of fetal malformations in humans are still unknown. Recent evidence suggests the relationship between environmental exposure to endocrine disruptors and fetal malformations. Our study aims to establish the role of Bisphenol A (BPA), if any, in altering human reproduction. We enrolled 151 pregnant women who were divided into two groups: case group (CS, n=101), women with established diagnosis of developmental defect, and control group (CL, n=50), pregnant women with normally developed fetus. Total, free and conjugated BPA were measured in their blood using GC-MS with isotopic dilution. The results show a correlation between environmental exposure to BPA and the genesis of fetal malformations. Conjugated BPA, which was higher in the CL, casts light on the hypothesis that a reduced ability to metabolize the chemical in the mother can concur to the occurrence of malformation. In a more detailed manner, in case of chromosomal malformations, the average value of free BPA appears to be nearly three times greater than that of the controls. Similarly, in case of central and peripheral nervous system non-chromosomal malformations, the value of free BPA is nearly two times greater than that of the controls.

Role of HbA1c in predicting risk for congenital malformations.

AIMS: Association between conventionally identified hyperglycemias and rates of congenital abnormalities is known; however there is less information about role of HbA1c in determining gestational hyperglycemias and associated risks. This study tried to explore the association between HbA1c in women without known diabetes at first antenatal visit and risk of congenital malformations (CM) among Saudi women living at Al-Madinah Al-Monawarah. METHODS: Eleven hundred and eighty (1180), healthy, first-trimester pregnant Saudi females without known diabetes, were selected from various antenatal care clinics of Al-Madinah Al-Monawarah city. General clinical and biochemical data was collected for this study by researchers at first visit and the time of delivery. RESULTS: Nearly one fifth (19.6%) of mothers had above normal HbA1c (>5.7) at first visit. Rates of CM had significant positive association with level of HbA1c. Rate of CM among those who had HbA1c in diabetes range, pre-diabetes range or normal range was 27.8%, 9.8% and 3.0%, respectively. The difference was significant between normal and pre-diabetes at the level P=0.000 and between pre-diabetes and diabetes at level P=0.038. CONCLUSION: In this study HbA1c is found to be a valuable predictor of risk of congenital malformations. This observation calls for further studies and establishment of policies for care of pregnant mothers having higher than normal HbA1c at first visit.

Congenital rickets due to vitamin D deficiency in the mothers.

BACKGROUND & AIMS: We wished to review all published reports of congenital rickets to identify the causes and characteristics. METHODS: 25 cases were identified in 19 published reports in which there was radiological and/or histological evidence of rickets in the first two weeks after birth. Cases of rickets associated with maternal renal failure were excluded as were infants born at less than 32 weeks gestation. RESULTS: There was evidence of maternal deficiency in 24 of these cases. In 16 cases the diagnosis of the rickets led to the identification of symptomatic osteomalacia in the mothers. Of the 12 mothers who had assays for serum 25-hydroxyvitamin D (25OHD) 11 had values less than 10 ng/mL. Presentations in the infants included craniotabes, wide skull sutures, rachitic rosaries, enlargement of the wrists, tetany and convulsions. In two cases rickets had been suspected from antenatal X-rays. In five cases fractures were found at the time of initial presentation. Of the 16 infants with serum calcium assays 15 had values lower than 8.8 mg/dL. Of 13 infants who had serum alkaline phosphatase assays 12 had abnormally high levels. Of the seven infants in whom serum 25OHD was measured before treatment, all had values less than 10 ng/mL. CONCLUSIONS: These reports provide strong support for the view that maternal deficiency leads to overt bone disease from before birth. Maternal deficiency probably also leads to impairment of bone quality in postnatal life. The importance of ensuring adequate vitamin D nutrition in pregnancy is emphasised.