Minor Congenital Malformations Research Articles

Post-Conceptional Exposure to Clomiphene Citrate and Congenital Malformations: A Cohort Study.

Clomiphene citrate is an ovulation inductor for which inadvertent post-conceptional exposures may occur in early pregnancy. In preclinical studies, post-conceptional exposures showed a teratogenic effect in different species. In humans, to date, little is known about the outcomes of inadvertently post-conceptionally exposed pregnancies. The objectives of our study were to assess the association between post-conceptional exposures to clomiphene citrate and major and minor congenital malformations in the offspring. A retrospective cohort study of prospectively ascertained cases was undertaken, based on clinical data from the Centre de Référence sur les Agents Tératogènes (CRAT), Paris, France. Women with post-conceptional exposure to clomiphene citrate (n = 309), and unexposed pregnant women (n = 1236, 1:4 ratio) with prospectively collected data, known pregnancy outcome and delivery date prior to 01/02/2022, were matched by calendar year. An adjudication committee classified major and minor congenital malformations according to the EUROCAT (European Registration of Congenital Anomalies and Twins) classification. Among post-conceptional exposed women, no increased risk of major malformation was found (crude relative risk = 0.64, 95% confidence interval 0.19-2.15) as compared to unexposed women. Three major and ten minor congenital malformations were reported in the exposed group. An increased risk of minor malformations was found (crude relative risk = 4.05, 95% confidence interval 1.70-9.64) although there was no specific clinical pattern. Post-conceptional exposure to clomiphene citrate was not associated with an increased risk of major congenital malformations. Given potential confounding and information biases, the results about minor malformations should be interpreted with caution as no specific clinical pattern was identified.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

Prenatal Exposure to Opioids and Neurodevelopmental Disorders in Children: A Bayesian Mediation Analysis.

This study explores natural direct and joint natural indirect effects (JNIE) of prenatal opioid exposure on neurodevelopmental disorders (NDDs) in children mediated through pregnancy complications, major and minor congenital malformations, and adverse neonatal outcomes, using Medicaid claims linked to vital statistics in Rhode Island, United States, 2008-2018. A Bayesian mediation analysis with elastic net shrinkage prior was developed to estimate mean time to NDD diagnosis ratio using posterior mean and 95% credible intervals (CrIs) from Markov chain Monte Carlo algorithms. Simulation studies showed desirable model performance. Of 11,176 eligible pregnancies, 332 had ≥2 dispensations of prescription opioids anytime during pregnancy, including 200 (1.8%) having ≥1 dispensation in the first trimester (T1), 169 (1.5%) in the second (T2), and 153 (1.4%) in the third (T3). A significant JNIE of opioid exposure was observed in each trimester (T1, JNIE = 0.97, 95% CrI: 0.95, 0.99; T2, JNIE = 0.97, 95% CrI: 0.95, 0.99; T3, JNIE = 0.96, 95% CrI: 0.94, 0.99). The proportion of JNIE in each trimester was 17.9% (T1), 22.4% (T2), and 56.3% (T3). In conclusion, adverse pregnancy and birth outcomes jointly mediated the association between prenatal opioid exposure and accelerated time to NDD diagnosis. The proportion of JNIE increased as the timing of opioid exposure approached delivery.

Adverse maternal outcomes associated with major fetal malformations after singleton live birth

Major fetal malformations complicate 2% to 5% of live births. It is unclear what effect fetal malformations have on severe maternal morbidity. This study aimed to compare maternal outcomes between individuals with a fetus with major or minor fetal malformations and those with a fetus without major or minor fetal malformations. This was a secondary analysis of the Consortium on Safe Labor database. Our study was limited to the current analysis of pregnant individuals with a singleton live birth. Major fetal malformations based on the Centers for Disease Control and Prevention's criteria were defined. Fetal malformations that did not meet the criteria for major fetal malformations were categorized as minor fetal malformations. Our primary maternal outcome was severe maternal morbidity as defined by the Centers for Disease Control and Prevention. Missing values were imputed by multiple imputation using the k-nearest neighbor imputation method. Poisson regression with robust error variance was used to obtain adjusted relative risks with 95% confidence intervals, controlling for confounders. Of 216,881 deliveries, there were 201,860 cases (93.1%) with no congenital malformation, 12,106 cases (5.6%) with minor fetal malformations, and 2845 cases (1.3%) with major fetal malformations. Compared with individuals with no fetal malformation, those with major fetal malformations were more likely to have severe maternal morbidity (0.7% vs 1.2%; adjusted relative risk, 1.51; 95% confidence interval, 1.07-2.12), postpartum hemorrhage (3.6% vs 6.9%; adjusted relative risk, 1.76; 95% confidence interval, 1.50-2.06), preeclampsia (5.1% vs 8.3%; adjusted relative risk, 1.48; 95% confidence interval, 1.31-1.67), and cesarean delivery (26.7% vs 42.3%; adjusted relative risk, 1.51; 95% confidence interval, 1.45-1.58). Compared with individuals with no fetal malformation, those with minor fetal malformations were more likely to have severe maternal morbidity (0.7% vs 1.4%; adjusted relative risk, 1.73; 95% confidence interval, 1.48-2.02), maternal death (0.01% vs 0.03%; adjusted relative risk, 4.50; 95% confidence interval, 1.18-17.19), postpartum hemorrhage (3.6% vs 6.1%; adjusted relative risk, 1.54; 95% confidence interval, 1.41-1.68), preeclampsia (5.1% vs 8.6%; adjusted relative risk, 1.50; 95% confidence interval, 1.41-1.60), superimposed preeclampsia (1.2% vs 2.4%; adjusted relative risk, 1.25; 95% confidence interval, 1.14-1.38), cesarean delivery (26.7% vs 39.6%; adjusted relative risk, 1.38; 95% confidence interval, 1.35-1.41), chorioamnionitis (3.0% vs 4.7%; adjusted relative risk, 1.41; 95% confidence interval, 1.29-1.53), and postpartum endometritis (0.6% vs 1.0%; adjusted relative risk, 1.58; 95% confidence interval, 1.31-1.90). Major and minor congenital fetal malformations are independent risk factors for severe maternal morbidity and other pregnancy complications.

P-293 Is time-lapse monitoring a safe alternative? Obstetric and neonatal outcomes of a multicenter randomized controlled trial

Abstract Study question Are there obstetric or neonatal risks associated with time-lapse monitoring and uninterrupted embryo culture compared to interrupted standard culture and conventional embryo selection? Summary answer The application of time-lapse monitoring using the Geri+ incubator is a safe alternative to standard culture and selection in terms of obstetric and neonatal results. What is known already There is very limited evidence regarding the safety of time-lapse monitoring (TLM) from prospective randomized controlled trials (RCT). Recent RCTs have demonstrated that the application of time-lapse monitoring does not increase (cumulative) live birth rates or the time to pregnancy within one year. However, while most studies only report pregnancy rates, it is essential to also study the safety of this commonly used method. Study design, size, duration The obstetric and neonatal outcomes of patients scheduled for day three single embryo transfer who participated in our multicenter RCT on TLM were studied. Three groups were compared: 1) TLE (Time-Lapse Eeva): embryo selection based on the Eeva® Test (a day three TLM algorithm, used adjunctively with morphology) and uninterrupted culture. 2) TLR (Time-Lapse Routine): routine morphological embryo selection and uninterrupted culture. 3) CON (Control): routine morphological embryo selection and interrupted culture. Participants/materials, setting, methods In total, 1731 IVF/ICSI patients undergoing their first, second or third oocyte pickup were randomized. Obstetric and neonatal data were registered for all pregnancies occurring after fresh and cryo embryo transfers associated with the initial oocyte pickup cycle as well as natural conceptions within one year. Adjusted relative risks with 95% CI were calculated; in view of the three groups and many comparisons only p-values are presented. Main results and the role of chance A total of 838 women had a live birth during the follow-up period (TLE = 281, TLR = 280, CON = 277; p = 0.98). The rate of serious pregnancy complications was not significantly different between the three groups (TLE = 10.7%, TLR = 10.9%, CON = 11.0%; p = 0.99). Mean gestational age at birth was 39.3 (2.0) weeks, 39.4 (1.6) weeks and 39.3 (2.0) weeks, respectively (p = 0.59). The rate of preterm and very preterm birth did not differ significantly between the three groups (<37 weeks: p = 0.50; <32 weeks: p = 0.20). Average weight at birth was 3396 (598) grams, 3394 (565) grams and 3363 (592) grams, respectively (p = 0.76). Low and very low birthweight also did not differ significantly between the three groups (<2500g: p = 0.77; <1500 g: p = 0.88). Health problems immediately after delivery were reported for eight babies in the TLE group, twelve in the TLR group and eleven in the CON group (p = 0.66). Major congenital malformations occurred in four children in the TLE group, four in the TLR group and seven in the CON group (p = 0.54). Minor congenital malformations were found in five children in the TLE group, three in the TLR group and five in the CON group (p = 0.73). No significant differences were observed for the mode of delivery and the APGAR scores. Limitations, reasons for caution This study reports the safety of time-lapse monitoring using the Geri+ time-lapse incubator, while more systems are currently available. Wider implications of the findings Uninterrupted embryo culture with or without the use of the Eeva® Test selection algorithm does not lead to increased obstetric or neonatal risks when compared to conventional interrupted embryo culture. Our results suggest that TLM is a safe and effective alternative to standard culture and selection. Trial registration number NTR5423

0909 Pitolisant Pregnancy Registry: An Observational Study of the Safety of Pitolisant Exposure in Pregnant Women and Their Offspring

Abstract Introduction WAKIX (pitolisant) is a potent and highly selective histamine 3 receptor antagonist/inverse agonist approved for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. The safety of pitolisant in pregnant women has not been established. Available case reports from clinical trials and postmarketing experience have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The registry is a prospective, observational cohort study designed to evaluate the association between pitolisant exposure during pregnancy and subsequent maternal, fetal, and infant outcomes. Methods The primary study population consists of 3 cohorts: pregnant women with a diagnosis of narcolepsy who are exposed to pitolisant during pregnancy, pregnant women with narcolepsy who are unexposed to pitolisant but exposed to comparator products during pregnancy, and pregnant women with narcolepsy who are neither exposed to pitolisant nor comparator products. Comparator products include modafinil, armodafinil, sodium oxybate, oxybate mixed salts, solriamfetol, methylphenidate, and amphetamines. Outcomes of interest include major congenital malformation (primary outcome), minor congenital malformation, pre-eclampsia, eclampsia, spontaneous abortion, stillbirth, elective termination, small for gestational age, preterm birth, postnatal growth deficiency, and infant developmental deficiency. Data are collected from enrolled pregnant women and healthcare providers involved in their care or the care of their infants, if applicable. Only data that are routinely documented in patients' medical records during usual care are collected. Participation in the registry is voluntary and participants may withdraw their consent to participate at any time. The registry design follows current FDA guidance for designing and implementing pregnancy exposure registries. Results The registry was initiated in May 2021. Presently, data are insufficient to assess an association between pitolisant exposure and any endpoint of interest. Study completion is planned in 2030. Conclusion Healthcare providers are encouraged to discuss this voluntary pregnancy registry with their eligible patients and assist women who are interested in enrolling. The study is registered on Clinicaltrials.gov (ID# NCT05536011). Support (if any) This study is sponsored by Harmony Biosciences LLC.

Exposure to duloxetine during pregnancy and risk of congenital malformations and stillbirth: A nationwide cohort study in Denmark and Sweden

The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths. A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates. Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.

Association of Chemotherapy Timing in Pregnancy With Congenital Malformation

Chemotherapy during the first trimester of pregnancy should be avoided owing to the risk of congenital malformations. However, the precise gestational age at which chemotherapy can be initiated safely remains unclear. To assess congenital malformation rates associated with gestational age at initiation of chemotherapy among pregnant women with cancer. This multicenter cohort study evaluated all pregnant women who received chemotherapy between 1977 and 2019 registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. Data were analyzed from February 15 to June 2, 2020. Cancer treatment with chemotherapy during pregnancy. Analysis was focused on major and minor structural malformations in offspring, defined by EUROCAT, detected during pregnancy or at birth. A total of 755 women in the INCIP database who underwent cancer treatment with chemotherapy during pregnancy were included in analysis. The median (range) age at cancer diagnosis was 33 (14-48) years. Among offspring, the major congenital malformation rate was 3.6% (95% CI, 2.4%-5.2%), and the minor congenital malformation rate was 1.9% (95% CI, 1.0%-3.1%). Chemotherapy exposure prior to 12 weeks gestational age was associated with a high rate of major congenital malformations, at 21.7% (95% CI, 7.5%-43.7%; odds ratio, 9.24 [95% CI, 3.13-27.30]). When chemotherapy was initiated after gestational age 12 weeks, the frequency of major congenital malformations was 3.0% (95% CI, 1.9%-4.6%), which was similar to the expected rates in the general population. Minor malformations were comparable when exposure occurred before or after gestational age 12 weeks (4.3% [95% CI, 0.1%-21.9%] vs 1.8% [95% CI, 1.0-3.0]; odds ratio, 3.13 [95% CI, 0.39-25.28]). Of 29 women who received chemotherapy prior to 12 weeks gestation, 17 (58.6%) were not aware of pregnancy, and 6 (20.7%) experienced a miscarriage (3 women [10.3%]) or decided to terminate their pregnancy (3 women [10.3%]). This cohort study found that chemotherapy was associated with an increased risk of major congenital malformations only in the first 12 weeks of pregnancy. The risk of congenital malformations when chemotherapy was administered during the first trimester and the high number of incidental pregnancies during cancer treatment in the INCIP registry underscore the importance of contraceptive advice and pregnancy testing at the start of chemotherapeutic treatment in young women with cancer.

Association of Gestational Opioid Exposure and Risk of Major and Minor Congenital Malformations

The rapid increase of opioid-related overdoses and deaths has become a public health concern in the US. Use of prescription opioids in pregnant women has increased; results from teratogenicity studies remain controversial. To evaluate the association between maternal prescription opioid use (excluding opioid use disorders) during pregnancy and the incidence of congenital malformations. This retrospective population-based cohort study evaluated linked Rhode Island Medicaid claims and vital statistics data of live births from January 1, 2008, to December 31, 2016. Data analysis was conducted from May 1, 2019, to May 31, 2020. Women who had a live birth during the study period, but no cancer or opioid use disorder, were followed up from 3 months before pregnancy to the end of pregnancy. Data on the mother's prescription opioid exposure were obtained through pharmacy claims and exposure was defined as dispensing of at least 1 prescription opioid during the first, second, or third trimester. The primary outcome was overall major or minor congenital malformations, defined as 1 or more major or minor congenital malformation. Secondary outcomes were defined as 10 specific categories of congenital malformations classified by organ systems using International Classification of Diseases diagnosis codes. Of 12 424 included pregnancies, 891 mothers (7.2%) received prescription opioids during pregnancy and 3153 infants (25.4%) were diagnosed with major or minor congenital malformations. Comparing prescription opioid exposure vs nonexposure, no excess risk was observed for major birth defects in infants with opioid exposure in trimester 1 (adjusted relative risk [aRR], 1.40; 95% CI, 0.84-2.34), and higher risks were found for overall minor birth defects in trimester 3 (aRR, 1.26; 95% CI, 1.04-1.53) and minor birth defects in the musculoskeletal system in trimester 2 (aRR, 1.50; 95% CI, 1.10-2.03) and trimester 3 (aRR, 1.65; 95% CI, 1.23-2.22). Significant dose responses in selected minor malformations and effects of specific opioids were also identified. Hydrocodone in trimester 2 (aRR, 3.01; 95% CI, 1.80-5.03) and oxycodone in trimester 3 (aRR, 2.43; 95% CI, 1.37-4.02) were associated with plagiocephaly, polydactyly, and other specified congenital deformities of the hip. The findings of this study suggest a higher risk of minor congenital malformations associated with use of prenatal prescription opioids in trimester 3, which seems to be dose-dependent. Further investigation is needed to establish causality and explore the physiologic plausibility of the association.

7q11.23 Microduplication Syndrome: Clinical and Neurobehavioral Profiling.

7q11.23 Microduplication (dup7q11.23) syndrome is a rare autosomal dominant disorder due to a recurring 1.5 to 1.8 Mb duplication of the Williams–Beuren Syndrome critical region. Dup7q11.23 has been associated with several neuro-behavioral characteristics such as low cognitive and adaptive functioning, expressive language impairment, anxiety problems and autistic features. In the present study, we analyze the clinical features of ten individuals in which array-CGH detected dup7q11.23, spanning from 1.4 to 2.1 Mb. The clinical characteristics associated with dup7q11.23 are discussed with respect to its reciprocal deletion. Consistent with previous studies, we confirm that individuals with dup7q11.23 syndrome do not have a homogeneous clinical profile, although some recurring dysmorphic features were found, including macrocephaly, prominent forehead, elongated palpebral fissures, thin lip vermilion and microstomia. Minor congenital malformations include patent ductus arteriosus, cryptorchidism and pes planus. A common finding is hypotonia and joint laxity, resulting in mild motor delay. Neuropsychological and psychodiagnostic assessment confirm that mild cognitive impairment, expressive language deficits and anxiety are recurring neurobehavioral features. New insights into adaptive, psychopathological and neurodevelopmental profiles are discussed.

CONGENITAL HIP DYSPLASIA HIGHLIGHTS OF AVASCULAR NECROSIS INCIDENCE AFTER OPEN REDUCTION FOR DEVELOPMENTAL DYSPLASIA OF THE HIP IN NAJAF (IRAQ)

Developmental dysplasia of the hip (DDH) is a one of the most common congenital abnormalities. It presents with the wide spectrum of anatomical features due to the mild or incomplete formation of the acetabulum leading to laxity of the joint capsule, secondary deformity of the proximal femur head and irreducible hip dislocation. It present with an estimated incidence ranging from 1.4 to 35.0 per 1000 newborns with higher prevalence in Asian, Mediterranean, Caucasian, and American populations with a sex-ratio of girls to boys as 4-10:1. The risk of complications after treatment is associated with the type of reduction and also depends of previous treatment and immobilization, degree of dislocation, patient’s age at surgery. This study is a cross-sectional study with DDH patients born between January 2018 and December 2019, in the city of Al Najaf, Iraq. Ethnicity, gender, fetal presentation, time of diagnosis, affected side of the hip, family history and avascular necrosis of the femoral head (AVN) complications were considered. Post-operative clinical and radiological evaluation was preformed depending on McKay’s criteria and Severin’s classification. A total of 49 DDH patients were identified with female:male ratio of 7,2:1. Among girls, the time of diagnosis was 2,68 ±1,14 years, in the group of boys this indicator was 3,4 ±1,02 years, р=0,231. In both gender group the bilateral process was most common (66,7% in male group and 58,9% in female group). In 30% patient the family history was positive. Normal vaginal delivery was in 69,4% cases (67,4 and 83,3% girls and boys). Breech presentation was observed exclusively in female group. In 14% cases a combination of DDH with other malformations was revealed, in most cases it was joint laxity, less common minor congenital malformations. In 30% patients the closed bilateral reduction was performed. 46 patients were undergoing open reduction. Complications of DDH were detected in 29% cases. Most common was avascular necrosis in varying degrees (35%), 14% patients had early osteoarthritis, 21% local infections. The post-operative clinical McKay’s criteria showed prevalence of excellent and good results. Findings of the post-operative radiographic assessment (Severins grade method) were excellent in 21 hips, good in 14 hips. Сonsequently, late diagnosis of DDH leads worth outcomes, requires surgical interventions and causes increasing frequency of complications.

CONGENITAL HIP DYSPLASIA HIGHLIGHTS OF AVASCULAR NECROSIS INCIDENCE AFTER OPEN REDUCTION FOR DEVELOPMENTAL DYSPLASIA OF THE HIP IN NAJAF (IRAQ)

Developmental dysplasia of the hip (DDH) is a one of the most common congenital abnormalities. It presents with the wide spectrum of anatomical features due to the mild or incomplete formation of the acetabulum leading to laxity of the joint capsule, secondary deformity of the proximal femur head and irreducible hip dislocation. It present with an estimated incidence ranging from 1.4 to 35.0 per 1000 newborns with higher prevalence in Asian, Mediterranean, Caucasian, and American populations with a sex-ratio of girls to boys as 4-10:1. The risk of complications after treatment is associated with the type of reduction and also depends of previous treatment and immobilization, degree of dislocation, patient’s age at surgery. This study is a cross-sectional study with DDH patients born between January 2018 and December 2019, in the city of Al Najaf, Iraq. Ethnicity, gender, fetal presentation, time of diagnosis, affected side of the hip, family history and avascular necrosis of the femoral head (AVN) complications were considered. Post-operative clinical and radiological evaluation was preformed depending on McKay’s criteria and Severin’s classification. A total of 49 DDH patients were identified with female:male ratio of 7,2:1. Among girls, the time of diagnosis was 2,68 ±1,14 years, in the group of boys this indicator was 3,4 ±1,02 years, р=0,231. In both gender group the bilateral process was most common (66,7% in male group and 58,9% in female group). In 30% patient the family history was positive. Normal vaginal delivery was in 69,4% cases (67,4 and 83,3% girls and boys). Breech presentation was observed exclusively in female group. In 14% cases a combination of DDH with other malformations was revealed, in most cases it was joint laxity, less common minor congenital malformations. In 30% patients the closed bilateral reduction was performed. 46 patients were undergoing open reduction. Complications of DDH were detected in 29% cases. Most common was avascular necrosis in varying degrees (35%), 14% patients had early osteoarthritis, 21% local infections. The post-operative clinical McKay’s criteria showed prevalence of excellent and good results. Findings of the post-operative radiographic assessment (Severins grade method) were excellent in 21 hips, good in 14 hips. Сonsequently, late diagnosis of DDH leads worth outcomes, requires surgical interventions and causes increasing frequency of complications.

Outcomes in three cases after brivaracetam treatment during pregnancy

Use of certain anti-seizure drugs (ASDs) during pregnancy increases the risk of major congenital malformations, while less is known about newer ASDs. Based on the safety of levetiracetam, brivaracetam may be similarly safe in pregnancy; however, no cases have been published to date. We retrospectively identified three women with epilepsy treated with brivaracetam during pregnancy and described the maternal and neonatal outcomes. We reviewed the patients' medical records as well as the linked medical records of their infants to identify complications during pregnancy and delivery, neonatal complications, and evidence of major/minor congenital malformations. Our series included one woman with idiopathic generalized epilepsy and two women with focal epilepsy (brivaracetam doses ranging from 50 mg - 200 mg daily). One patient with focal epilepsy experienced breakthrough seizures and lamotrigine was added to brivaracetam. The other women had no neurologic complications during pregnancy. All three women had full term deliveries without significant complications. Three healthy infants were born with Apgar scores of 9 and 9 and no major congenital malformations. Three minor congenital malformations were observed in two infants. While the absence of major congenital malformations in these cases is encouraging, further data are needed to determine the safety of brivaracetam in pregnancy.

A case of de novo 18p deletion syndrome with panhypopituitarism.

Deletion on the short arm of chromosome 18 is a rare disorder characterized by intellectual disability, growth retardation, and craniofacial malformations (such as prominent ears, microcephaly, ptosis, and a round face). The phenotypic spectrum is wide, encompassing a range of abnormalities from minor congenital malformations to holoprosencephaly. We present a case of a 2-year-old girl with ptosis, a round face, broad neck with low posterior hairline, short stature, and panhypopituitarism. She underwent ventilation tube insertion for recurrent otitis media with effusion. Brain magnetic resonance imaging showed an ectopic posterior pituitary gland and a shallow, small sella turcica with poor visualization of the pituitary stalk. Cytogenetic and chromosomal microarray analysis revealed a de novo deletion on the short arm of chromosome 18 (arr 18p11.32p11.21[136,227–15,099,116]x1). She has been treated with recombinant human growth hormone (GH) therapy since the age of 6 months after diagnosis of GH deficiency. Her growth rate has improved without any side effects from the GH treatment. This case expands the phenotypic spectrum of 18p deletion syndrome and emphasizes the positive impact of GH therapy on linear growth in this syndrome characterized by growth deficiency. Further studies are required to define the genotype-phenotype correlation according to size and loci of the deletion in 18p deletion syndrome and to predict prognosis.

Maternal antibiotic exposure and fetal outcomes: is there evidence for teratogenicity?

Aim: During pregnancy, untreated infections may be associated with low birth weight, preterm birth, and spontaneous abortion. Thus, use of antibiotics are commonly seen in pregnancy. In this study, we aimed to evaluate the possible teratogenic risks related to the maternally exposed antibiotics during pregnancy. Material and Methods: Data from pregnant women, who used antibiotics for several infectious diseases between 2014 and 2018, and admitted to our Teratology Information Service for drug analysis, were collected. Data concerning their medication, concomitant drugs and co-morbidities were documented. The possible teratogenic risks related to the drugs were evaluated. A follow-up was conducted with the women after delivery to obtain whether any major or minor congenital malformations occurred in the infants.Results: The maternal use of doxycycline between 3-6th weeks, and acyclovir between 1-2nd weeks of pregnancy resulted in elective termination. The maternal use of cefazoline between 3-4th weeks of pregnancy, and the use of amoxicillin-clavulanate between 3-6th weeks of gestation resulted in spontaneous abortion. In the outcome of one pregnancy, the concomitant exposure of miconazole, metronidazole, ciprofloxacin, ornidazole and isoconazole in the first two weeks of pregnancy resulted in hypothyroidism in the infant. Conclusions: Antibiotics presented no major teratogenic effects. However, their use in pregnancy should be used only when indicated. Pregnant women should have access to the information and specific advice on the use of medications with proven safety in pregnancy through counseling with the Teratology Information Services.

Pregnancy outcomes after maternal betahistine exposure: A case series

ObjectiveTo investigate the pregnancy outcomes of women who were exposed to betahistine during their pregnancies. MethodsWe identified and evaluated the outcomes of 27 pregnant women who were referred to Terafar (Teratology Information Service, Izmir, Turkey) for a teratological risk assessment. ResultsOf 24 pregnancies with known outcomes, 21 resulted in live births (including two pairs of twins) whereas two ended with miscarriage and three with elective terminations. Among the 20 live births for whom the malformation details were available, there were 17 normal outcomes, one major and two minor congenital malformations. ConclusionsDespite a number of limitations, this case series may be of value regarding counseling pregnant women with inadvertent betahistine exposure. Further epidemiological studies with larger sample sizes and control groups are necessary to draw more definite conclusions.

Pregnancy outcomes after maternal use of thiocolchicoside: A case series

ObjectiveThe 2014 report by European Medicines Agency (EMA) restricted the use of thiocolchicoside for all reproductive-age women. In this study, we aim to expand the systematically-collected human data and discuss it within the frame provided by this report. MethodsWe identified and evaluated the outcomes of 48 prospectively recorded pregnancies referred to Terafar (Teratology Information Service, Izmir, Turkey). ResultsOf 42 pregnancies with first-trimester exposure and known outcomes, 31 resulted in live births, four in miscarriage and seven ended with elective terminations. There were 26 normal outcomes, two major and three minor congenital malformations among the live births. ConclusionsDespite a number of limitations, our results and previous case series collectively strengthen the view that thiocolchicoside is unlikely to be a major teratogen. EMA’s 2014 report should be revised to reflect this finding, while current restrictions on use should continue until more detailed safety information is available.

Teratogenic evaluation of drugs used by pregnant patients with gastrointestinal system diseases

Aim: Drug use may be necessary in pregnant women due to chronic diseases or digestive disorders. However, safety of the use of many medications during pregnancy remains limited. The purpose of this study is to evaluate the safety of digestive system drugs during pregnancy. Material and Methods: In this observational study, we collected data of pregnant women who used gastrointestinal agents between 2014 and 2018. Data regarding the medications, exposure to other agents and co-morbidities were documented. Our Teratology Information Service assessed the teratogenic risk of drugs. To investigate the pregnancy outcomes, a follow-up was conducted on the women after delivery to obtain whether there had been any major and/or minor congenital malformations and/or adverse neurodevelopmental effects in the infant. Results: Twelve pregnant women (age 27-34 years), whose gestational age were between 4 and 24 weeks at admission time, were followed up. Among patients, one woman with ulcerative colitis used azathioprine; two women with hepatitis B using tenofovir; three women with nausea and abdominal pain used metoclopramide, hyoscine, ondansetron; six women with dyspepsia and gastritis used alginic acid, antacids, lansoprazole, rabeprazole, pantoprazole, trimebutine, alverine and pancreatin. After delivery, no congenital anomalies were detected. Two infants had low birth weights for gestational age, and one was born preterm. Conclusion: Data in our study contributes to the literature on safety of gastrointestinal system medications in pregnancy. This permits decreasing the number of potential elective terminations related to the concerns about digestive system drugs.

Predictive factors of early postoperative respiratory complications after tonsillectomy in children with unidentified risks for this complication

IntroductionTonsillectomy is considered as a therapeutic option in obstructive sleep apnoea syndrome (OSAS). Postoperative respiratory failure is a complication that can require respiratory support. The main objective of our study is to determine risk factors of postoperative respiratory complications in children undergoing tonsillectomy. Material and methodsThis is a retrospective single centre observational study including patients with unanticipated postoperative respiratory failure. Patients with a planned preoperative intensive care admission were excluded (age is lower than 2 years, overweight (>95% percentile of BMI), moderate or severe asthma, major medical conditions). Those patients were compared with randomly selected control patients. Factors studied were: age, weight, indication of surgery, ASA status, preoperative illness conditions, durations of surgery and anaesthesia and administered medications. Statistics used a univariate analysis and a multivariate logistic regression. ResultsEight hundred and five patients underwent adenotonsillectomy during the study period and 25 developed postoperative respiratory failure. These patients were compared to 103 non-complicated control patients. Age (<4 years), weight (<18kg), indication of surgery (as SOAS), laryngomalacia, stable and minor congenital cardiac malformation and duration of anaesthesia were found statistically associated. Multivariate analysis found that weight <18kg is a risk factor associated with the occurrence of postoperative respiratory failure. Overall the model shows a strong accuracy with an area under the curve of ROC analysis of 0.9 [95% confidence interval: 0.85–0.95]. DiscussionOur study found that weight <18kg is a major risk factor for predicting a postoperative respiratory complication.

Preferences of Pregnant Women With Cardiac Disease for Maternal-Fetal Outcomes Related to Their Pregnancies [20N

INTRODUCTION: The trade-offs pregnant women with cardiac disease are willing to make in order to optimize pregnancy outcomes is undetermined. This study aimed to elicit preferences of these women for maternal and fetal outcomes related to cardiac disease in pregnancy. METHODS: A cross-sectional study was conducted on pregnant women with cardiac disease. participants were then presented with 19 vignettes describing combined maternal and fetal outcomes related to cardiac disease. Maternal outcomes included cardiac events (arrhythmias and cardiac failure), blood clots, a combination of the two and no cardiac events; while fetal outcomes included perfect health, minor or major malformations, small-for-gestational-age (SGA) infants and fetal demise. Participants were asked to assign values to these outcomes on a visual analogue scale (VAS), by the standard gamble (SG) and time trade-off (TTO) methods. Utility values (preferences) for each state obtained from all three methods were presented on a scale of 0-100. RESULTS: 34 pregnant women with cardiac disease completed the interviews. The median age was 31.5 [29-34] years and the median gestational age was 24 [19-35] weeks. Participants did not perceive combinations of maternal cardiac events as more severe than a solitary event. Also, they regarded SGA as more severe outcome than minor congenital malformations, but valued major malformations as bad as fetal demise. CONCLUSION: This study is the first to obtain preferences of pregnant women with cardiac disease for combined maternal and fetal outcomes related to their condition. These preferences should be incorporated in clinical decision-making.