Malformations In Infants Research Articles

Increased rate of major malformations in offspring exposed to valproate during pregnancy

To determine the rate of occurrence of major malformations in infants whose mothers had taken the drug valproic acid (VPA) as monotherapy during the first trimester of pregnancy and had enrolled in the North American Antiepileptic Drug Pregnancy Registry. Data were collected from pregnant women throughout the United States and Canada through telephone-based interviews. Each woman was interviewed at enrollment, at 7 months' gestation, and postpartum. With her written permission, the medical records of each mother and her infant were obtained. The major malformations tabulated were those identified at or before 5 days of age. The prevalence of congenital malformations among offspring of monotherapy VPA-exposed women was compared with that among infants of women exposed to all other antiepileptic drugs (internal comparison group) and with that among newborns in the Active Malformations Surveillance Program at Brigham and Women's Hospital (external comparison group). Sixteen affected cases were identified among 149 VPA-exposed women (proportion: 10.7%; 95% CI: 6.3 to 16.9%). The prevalence in the internal comparison group was 2.9% (95% CI: 2.0 to 4.1%; odds ratio: 4.0, 95% CI: 2.1 to 7.4; p < 0.001). Assuming a 1.62% prevalence in the external comparison group, the relative risk of having an affected offspring for VPA-exposed women was 7.3 (95% CI: 4.4 to 12.2; p < 0.001). Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations.

Detection and prevention of neurologic injury in the intensive care unit

Survivors of repairs of complex congenital cardiac malformations in infancy have an increased risk of permanent abnormalities in motor, cognitive, expressive, and behavioral functioning. These functional deficits are expressions of complex interactions of environment, including prolonged hospitalization and conditioned child–parental behaviours, alterations of social environment, the effects of physical limitations, biological influences including genetic determinants, prenatal injury, and acquired reversible and irreversible neuronal injury.1,2 The magnitude of the problem is large, with incidence dependent upon the measures used for assessment. Overt postoperative neurologic signs have been recorded in up to one-tenth of postoperative infants and children, with double that rate found in those with abnormalities of the aortic arch.3 A decreased potential for development, based upon parent-sibling models, has been estimated to occur in one-third of survivors.4,5 Evidence of injury is provided by magnetic resonance imaging in up to one-third of patients preoperatively, and between half and nine-tenths postoperatively, although most of these early postoperative changes will disappear.5 Although recent changes in perioperative management are likely to reduce such neurologic injury, their significance remains high.

Quality of life following surgery for congenital cardiac malformations in neonates and infants

The past two decades have witnessed a major shift towards repair of most congenital cardiac malformations during the neonatal or infant periods of life.1 Early anatomic correction or palliation, dramatic improvements in survival, and reduced morbidity due to improvements in perioperative and long-term medical management, have resulted in new populations of children that have reaped the benefits of the best care currently available for treatment of congenital cardiac disease. The impact of the congenital cardiac malformations, however, extends far beyond the walls of the hospital or clinic where we diagnose, treat, and follow our patients. The breakthrough of achieving predictable results with repair or palliation of most lesions during the neonatal and infant periods mandates us to look beyond survival, and to examine the lives our patients lead when they are outside of our care. Our purpose in this review is to discuss the measures of psychosocial outcome that are appropriate for exploration in those neonates and infants who survive cardiac surgery, to explore what is known about the psychosocial outcomes and quality of life for these patients, and what needs exist for future research.

In vitro fertilization (IVF) in Sweden: Risk for congenital malformations after different IVF methods

The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk.

Tibial Hemimelia, Preaxial Polydactyly, and Vertebral Anomalies: A Pattern of Malformations in Infants of Diabetic Mothers

Tibial Hemimelia, Preaxial Polydactyly, and Vertebral Anomalies: A Pattern of Malformations in Infants of Diabetic Mothers

Severe Adverse Effects in a Newborn with Two Defective CYP2D6 Alleles After Exposure to Paroxetine During Late Pregnancy

Paroxetine, like other SSRIs, is reported not to increase the number of malformations in infants exposed to these drugs in utero. However, late pregnancy exposure to SSRIs sometimes leads to perinatal complications resembling the symptoms seen in serotonergic overstimulation. We report here a case of third trimester paroxetine exposure with adverse birth outcome in a newborn. The clinical symptoms in the infant included severe tremor and rigidity as well as loose stools during the first 4 days of life. Plasma paroxetine concentrations in infant plasma were quite low after birth, but she was genotyped to be a poor metabolizer of CYP2D6, the enzyme catalyzing the metabolism of paroxetine. In accordance with an earlier report, we suggest that even low plasma concentrations of paroxetine may be related to perinatal complications in infants exposed to paroxetine during late pregnancy and that the poor metabolizer genotype of CYP2D6 may be a risk factor for these complications.

Occupational Gonadal and Embryo/Fetal Doses From Fluoroscopically Assisted Surgical Treatments of Spinal Disorders

Simulation of lumbar spine fluoroscopy used during surgical treatments of spinal disorders on a humanoid phantom and monitoring of the scattered radiation levels. To assess the potential of adverse effects to progeny due to the preconceptual and embryo/fetal exposure to ionizing radiation resulting from the parental occupational exposure to scattered radiation from lumbar fluoroscopy. There are no available data on embryo/fetal doses resulting from maternal occupational exposure in the orthopedic theater. Besides, studies on staff gonadal doses from fluoroscopically assisted spine surgery are scarce and their results are not generally applicable. Lumbar spine anterior-posterior and lateral fluoroscopy were performed on an anthropomorphic phantom. Scattered radiation within the orthopedic theater was recorded at the staff genitals and waist level. Gonadal, abdominal surface, and embryo/fetal doses normalized to the dose-area-product specific to each projection were calculated. If the annual dose limits of occupational exposure are continuously exhausted for 10 years, the resulting radiogenic risk of congenital malformation in infants born to the orthopedic theater staff will be at least two orders of magnitude lower than the corresponding spontaneous probability. The occupational exposure of the pregnant mother bears a negligible contribution to the risk of hereditary effect on the newborn's progeny compared with the natural incidence rate. Radiogenic genetic and embryo/fetal risks resulting from occupational exposure due to fluoroscopically assisted surgical treatments of spinal disorders are well within tolerance levels provided that rigorous confinement to all pertinent occupational dose constraints is established.

Cardiovascular malformations and sudden death in infancy.

We survey the postmortem findings of cardiovascular malformations in infants under the age of 1 year who died suddenly and unexpectedly, in a way that mimicked sudden infant death syndrome (SIDS), and evaluate the importance of the malformation for the fatal outcome. Four hundred fifty-seven infants under the age of 1 year, who died between 1982 and 2001, were investigated at the Department of Forensic Medicine in Stockholm, Sweden. Cardiovascular malformations were found in 18 infants (3.9%). Only 6 of 18 malformations, mostly severe, were clinically diagnosed before death. In the other 12 infants, cardiovascular malformations were found, such as atrial or ventricular septal defects, coarctation of aorta, stenosis of the aortic or pulmonary artery orifice, and aneurysm of the membranous portion of the interventricular septum. In all instances, the heart weight was increased. The observation of undiagnosed cardiovascular malformations as the only explanation for the cause of sudden and unexpected death in apparently healthy infants may advocate more examinations of the infant during early life. It is also important to enlarge the debate of the cause of death in infants with cardiovascular malformations. Should they be included in borderline SIDS?

Possible association between different congenital abnormalities and use of different sulfonamides during pregnancy.

The objective of the study presented here was to check the debated human teratogenic potential of sulfonamide drugs. Five different sulfonamides such as sulfamethazine, sulfathiourea, sulfamethoxypyridazine, sulfamethoxydiazine and the combination of sulfamethazine-sulfathiourea-sulfamethoxypyridazine were differentiated. Cases with congenital abnormalities were compared with their matched controls without congenital abnormalities in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996. Of 38,151 newborn infants without any congenital abnormalities (control group), 163 (0.4%) had mothers who were treated with the sulfonamides studied during pregnancy, while of 22,843 cases with congenital abnormalities, 140 (0.6%) had mothers who were treated with the sulfonamides studied during pregnancy. The analysis of cases and matched controls indicated a higher rate of cardiovascular malformation (adjusted prevalence odds ratios [POR] with 95% CI: 3.5, 1.9-6.4) and clubfoot (adjusted POR with 95% CI: 2.6, 1.1-6.2) in infants born to mothers with sulfonamide treatment in the second and third months of pregnancy. The detailed analysis of different sulfonamides showed a possible association between cardiovascular malformations (adjusted POR with 95%; CI: 6.5, 2.6-15.9), particularly ventricular septal defect (17.1, 1.3-141.1) and sulfamethoxydiazine during the second and third months of pregnancy. In addition, a possible association was found between clubfoot and sulfathiourea, both during the entire pregnancy (adjusted POR with 95% CI: 2.3, 1.2-4.3) and in the second and third months of gestation (3.9, 1.1-13.8). Thus, maternal treatment of sulfamethoxydiazine may cause ventricular septal defect, while sulfathiourea may induce clubfoot; however, further studies are needed to verify or reject these associations.

Transperineal sonography in anorectal disorders

Magnetic resonance imaging, computed tomography, endorectal and endoanal sonography are used for imaging of inflammatory and neoplastic conditions of the lower rectum, the anus and the perineum. These methods, however, have their limitations regarding accuracy, cost-effectiveness, and availability in the acute setting. Pain may be a limiting factor when introducing a probe into the anus. Percutaneous transperineal sonography is an acknowledged method for diagnosing anorectal malformations in children and infants and for diagnosis of prostatic disease. Until today, only limited reports regarding the value of transperineal sonography for evaluation of diseases of the lower rectum, the anus and the perianal region in adults are available. Between 1997 and 2000 a total of 44 patients underwent transperineal sonography including B-mode and colour Doppler sonography for imaging anorectal structures using 3.5 MHz sector arrays and 7 MHz linear arrays. The lesions were also investigated using colour Doppler imaging. During examination the patient is positioned on his side. Orientation landmarks are the pubic symphysis and the prostate gland in men and the vagina in women. The spectrum of diseases of the current study population (44) included perianal fistulas (10), pararectal abscesses (7), fistulas with abscess (7), perianal inflammation without abscess (1), rectal (6) and anal carcinomas (3) and metastasis of a leiomyosarcoma (1). In 10 cases digital examination of the anus and rectum was not possible because of intense pain. In 34 patients (85 %) sonographic findings were confirmed by intraoperative diagnosis. Transperineal sonography proved to be an inexpensive, easily available diagnostic tool that may help in detecting a variety of pathological conditions of the lower rectum, the anus, and the perianal region.

Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: a nation‐wide, population‐based register study

Aim: Antiepileptic drugs (AEDs) are known teratogens. Some specificity between different AEDs has been noted in the literature. The aim was to compare the teratogenic effect of valproic acid (VPA) and carbamazepine (CBZ) in monotherapy. Methods: Infants exposed to AEDs (n= 1398) in early pregnancy were identified from the Swedish Medical Birth Registry. The number of infants with congenital malformations and exposed to AED was compared with the expected number estimated from all infants born (n= 582656). Results: 90% (1256) of the AED exposed children were exposed to AEDs in monotherapy, 56% were exposed to CBZ and 21% to VPA. The odds ratio (OR) for having a malformation in the AED exposed group was 1.86 [95% confidence interval (95% CI) 1.42‐2.44]. Exposure to VPA in monotherapy compared with CBZ in monotherapy gave OR = 2.51 (95% CI 1.43‐4.68) for a neonatal diagnosis of malformations. However, there is no information available on the number of therapeutic abortions, or the different types of epilepsy or drug dosage in the two treatment groups. Conclusion: There was a small increase in the risk of having a major malformation after exposure to AEDs in monotherapy. Exposure to VPA seems to carry a higher risk than exposure to CBZ.

Metoclopramide for Nausea and Vomiting of Pregnancy: A Prospective Multicenter International Study

Berkovitch, Matitiahu; Mazzota, Paul; Greenberg, Revital; Elbirt, Daniel; Addis, Antony; Schuler-Faccini, Lavinia; Merlob, Paul; Arnon, Judy; Stahl, Bracha; Magee, Laura; Moretti, Myla; Ornoy, Asher

Maternal diabetes mellitus and infant malformations

OBJECTIVE: To investigate the effects of pregestational, as opposed to gestational, diabetes on infant malformations. METHODS: All women delivering infants at Parkland Hospital between January 1, 1991, and December 31, 2000, were ascertained. Screening for gestational diabetes was methodically employed throughout the study period using National Diabetes Data Group criteria for diagnosis of pregestational and gestational diabetes. Standardized definitions of major infant malformations were specified before data analysis and subdivided according to the organ systems involved. RESULTS: A total of 145,196 women were delivered during the study period, and 2687 (1.9%) were diagnosed to have diabetes mellitus. Gestational diabetes was diagnosed in 2277 (1.6%) of whom 230 (10%) had fasting hyperglycemia diagnosed, and the remainder consistently demonstrated fasting serum levels less than 105 mg/dL. Pregestational diabetes was diagnosed in 410 (0.3%) women. Infant malformations occurred in 1.5% of nondiabetic women compared with 1.2% of women with normal fasting glucose gestational diabetes, 4.8% in women with gestational diabetes plus fasting hyperglycemia, and 6.1% in those with pregestational diabetes ( P < .001, for comparison of the latter two groups with the nondiabetic population). CONCLUSION: Women with pregestational diabetes or gestational diabetes plus fasting hyperglycemia have a three- to four-fold increased risk of infant malformations, whereas women with mild gestational diabetes have malformation rates no different than the general nondiabetic obstetric population.

Discussion

True high-flow arteriovenous malformations (AVMs) of the maxilla and mandible are rare. 1 Kaban LB Muliken JB Vascular anomalies of the maxillofacial regions. J Oral Maxillofac Surg. 1986; 44: 203 Abstract Full Text PDF PubMed Scopus (129) Google Scholar , 2 Muliken JB Glowacki J Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg. 1982; 69: 412 Crossref PubMed Scopus (2606) Google Scholar However, when present, they can be a challenge to treat. In this article, the authors present 5 cases in which high-flow AVMs of the maxilla and mandible were treated by direct puncture and coil embolization. This technique in which the AVM is entered through a direct puncture of the bone or an extraction site has been previously described as an alternative to other treatment modalities. 3 Perrott DH Schmidt B Dowd CF et al. Treatment of a high-flow arteriovenous malformation by direct puncture and coil embolization. J Oral Maxillofac Surg. 1994; 52: 1083 Abstract Full Text PDF PubMed Scopus (31) Google Scholar , 4 Resnick SA Russell EJ Hanson DH et al. Embolization of a life-threatening mandibular vascular malformation by direct percutaneous transmandibular puncture. Head Neck. 1992; 14: 372 Crossref PubMed Scopus (40) Google Scholar , 5 Teitelbaum GP Halbach VV Fraser KW et al. Direct puncture coil embolization of maxillofacial high-flow malformation. Laryngoscope. 1994; 104: 1397 Crossref PubMed Scopus (11) Google Scholar

Use of folic acid and delivery outcome: a prospective registry study

Periconceptional use of folic acid is thought to reduce the risk for both neural tube defects and other congenital malformations. Most published data were obtained retrospectively. We used the Swedish Medical Birth Registry to study congenital malformations in infants born of women who reported the use of folic acid in early pregnancy (of which 70% probably used it also preconceptionally) and compared them with population rates. We divided the material according to two major confounders: subfertility problems and use of antiepileptic drugs. We found no protective effect of folic acid tablet use on the rate of congenital malformations but data on neural tube defects were scarce. Our results support the scepticism recently expressed in the literature on the beneficial effect of folic acid in preventing congenital malformations, especially of a non-neural tube defect type.

A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991-1998).

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.

A Population-Based Study on the Frequency of Additional Congenital Malformations in Infants with Congenital Hypothyroidism: Data from the Italian Registry for Congenital Hypothyroidism (1991-1998)

A Population-Based Study on the Frequency of Additional Congenital Malformations in Infants with Congenital Hypothyroidism: Data from the Italian Registry for Congenital Hypothyroidism (1991-1998)

Oral antihyperglycemic agents during pregnancy and lactation: a review.

The treatment approach of diabetes mellitus during pregnancy requires a combination of diet, exercise, multiple home glucose determinations and intensive insulin regimens. During the last decade there was an increased interest in the use of oral antihyperglycemic agents (OAHAs) as an alternative to insulin in achieving good glycemic control. OAHAs are divided into four groups: derivatives of sulfonylurea, biguanides, glucosidase inhibitors and thiazolidinediones. This review describes the possible teratogenic effects of the use of OAHAs during pregnancy and the effects of these drugs during lactation. Animal and human studies assessing the teratogenic effects of OAHAs have yielded conflicting data because the risk of major malformations in infants of mothers with diabetes appears to be related to maternal glycemic control rather than the antidiabetic therapy. A major concern with the use of OAHAs during pregnancy is neonatal hypoglycemia, which may be severe and persist for days. Therefore, insulin is still the drug of choice because it has not been implicated as a teratogen in human pregnancies. In addition, because of the lack of data regarding the use of OAHAs in pregnancy, we cannot draw firm conclusions about all of the available drugs. However, OAHAs, especially glibenclamide (glyburide), may be beneficial in a situation where the proper use of insulin is problematic. Because there are very limited clinical data on the exposure of OAHAs to the infant via breast milk, and the potentially serious effect of neonatal hypoglycemia, the safest recommendation is not to breast feed while taking OAHAs. Well-conducted, prospective, controlled studies regarding the feasibility of OAHAs in pregnant women with diabetes and during lactation are needed.

CONGENITAL ANOMALIES AMONG INFANTS OF DIABETIC MOTHERS

SUMMARY Congenital anomalies are the most common cause of perinatal mortality in infants of diabetic mothers. Late fetal loss and metabolic abnormalities also feature in increased perinatal mortality due to maternal diabetes. Maternal hyperglycemia during early gestation is associated with an increased frequency of structural defects. Four infants who were admitted to the Neonatal Intensive Care Unit (NICU) of our institution are presented here in a discussion of rare congenital malformations in infants of diabetic mothers.

Nonsteroidal anti-inflammatory drugs in early pregnancy

A study was performed of congenital malformations in infants whose mothers used nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy. Data were obtained from an ongoing prospective recording of drug use during the first trimester. During the period July 1, 1995 through December 31, 1998, 2557 infants were born to women who reported the use of NSAIDs in early pregnancy. The OR (after consideration of maternal age, parity, and smoking habits) for any congenital malformation was 1.04 (95%CI 0.84–1.29), but the OR for cardiac defects reported to the Medical Birth Registry was 1.86 (1.32–2.62) based on 36 instances, and for orofacial clefts 2.61 (1.01–6.78) based on only six instances. By using other information sources, another four infants with cardiac defects were identified. There was no drug specificity for cardiac defects but among six mothers of infants with orofacial clefts, five had used naproxen.