Higher Rates Of Congenital Malformations Research Articles

Prematurity and congenital malformations differ according to the type of pregestational diabetes

BackgroundDiabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM.MethodsSingle-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected.ResultsAs expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI.ConclusionsNewborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications.

Gestational Exposure to Serotonin Reuptake Inhibitors and Pregnancy Outcome; Exploring the Role of Bias and Confounders.

There is no other example in human teratology where, after more than 40 epidemiological studies, repeated meta-analyses and thousands of pregnancies, the fetal safety or risk of an agent has not been verified and settled.The objectives of the present review were to identify and discuss sources of bias that may lead clinicians and scientists to believe that SRIs cause malformation or other adverse outcomes, where, in fact, they may not.The present study highlights sources of bias that may explain why children exposed in utero to SRI exhibit higher rates of congenital malformations, mostly cardiovascular and other complications. It appears that pregnant women treated for depression and anxiety are distinctively different from healthy women in numerous covariates, which may confound pregnancy outcomes. Acknowledging and adjusting for these sources of bias are critical before one selects to withhold therapy for moderate or severe cases of depression and anxiety in pregnancy.

Adverse perinatal outcome in teenage pregnancies: an analysis of a 5-year period in Southeastern Hungary

Objective: To determine the risks of adverse perinatal outcomes of teenage mothers.Material and methods: A retrospective analysis was performed on teenage mothers (under 20 years of age) who delivered in the period of 2010–2014 at the Department of Obstetrics and Gynecology, University of Szeged (study group). All mothers who delivered in Hungary during the same period were studied as a control group. The following parameters were analyzed: demographic data of the mothers, maternal complications, perinatal outcome and congenital malformations of the newborns. The binominal test, Student’s t-test and Poisson’s regression were applied using STATA 9.0 (StataCorp, College Station, TX, USA) statistical software (p < .05 was considered to be statistically significant).Results: During this 5-year period, 12,845 births were recorded at the Department, of these 274 (2.1%) were teenage pregnancies with 275 newborns. The offsprings of teenage mothers had significantly lower mean birth weight (3110.2 ± 564.03 g versus 3247 g), higher rate of congenital malformations (8.0 versus 5.0%) and higher admission to neonatal intensive care unit (12.4 versus 8.0%) than the infants in the control group.Conclusions: Younger maternal age was significantly associated with lower mean birth weight, higher risk of congenital malformations, and increased admission rate to neonatal intensive care unit.

Incidence and distribution of congenital malformations in newborns: a hospital based study

Background: It is considered that the congenital disorders are not a public health problem among the developing countries, however, over the recent years, they are actually experiencing a transition in the epidemiology like significant reduction in infant mortality rates, decline in infections and malnutrition and also a relative rise in morbidity as well as mortality due to the congenital malformations. Present study describes the incidence and distribution of congenital malformations in newborns during the study period at Government Medical College and Hospital, Aurangabad, Maharashtra, India. Methods: This study was a hospital based cross sectional study. Seven thousand and twelve (7012) babies born over a period extending from 1 st March 1994 to 31 st April 1995 at Government Medical College and Hospital, Aurangabad, Maharashtra were studied for congenital malformations diagnosed clinically within 3 days of life. Both major and minor malformations were recorded. Minor variations such as capillary haemangioma, mongolian spots, superficial sacral dimples, small umbilical hernias, saddle nose, mild bowing of tibia and hydrocele of the testis were not considered as malformation. Results: Out of 7012 subjects, 66 newborns (0.94%) were found to be affected with congenital malformations. There was no statistically significant difference between the incidence of congenital malformations in males and females with a male: female ratio of 0.97:1. Central nervous system malformations were the most common and found in 51.66% cases. There was statistically significant higher rate of congenital malformations among stillborn babies (8.54%) as compared to live born babies (0.62%) with a p value less than 0.05. Out of 66 newborns with congenital malformations, 19 newborns had other birth defects apart from the congenital malformation. Conclusions: Congenital malformations were noted in 0.94% of the newborns at the tertiary care hospital and central nervous system malformations were the most common.

Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: a cohort study

ObjectivesSecond-generation antipsychotics (SGAs), in conjunction with other psychotropic medications, are increasingly used to treat psychiatric disorders in pregnancy. The few available studies investigating the reproductive safety of SGAs did not...

Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China

Previous studies inconsistently suggest that assisted reproduction technology (ART) may increase the risk of birth defects in children. Live birth infants, conceived by in vitro fertilization fresh embryo transfer (IVF), intracytoplasmic sperm injection fresh embryo transfer (ICSI), or frozen-thawed embryo transfer (FET) in Reproductive Center of Tongji Hospital (Wuhan, China) between 1997 and 2008, were followed up at birth and after 3 years. Preterm pregnancy, multiple pregnancy, sex ratio (male/female), congenital malformation were compared. A total of 4,236 children were born after ART (IVF 2,543, ICSI 908, FET 785). Compared with IVF, the rate of preterm pregnancy and sex ratio in ICSI were lower (p < 0.05); the rate of multiple pregnancy in ICSI and FET were all lower than IVF (p < 0.05). Congenital defects were comparable in all groups at birth. In total, 2,908 children participated in the second follow-up from 34 months to 60 months with an average of 40 months, and the cases of birth defects had doubled (3 years: 5.16%, birth: 2.22%). The birth defect rate in boys conceived through ICSI was significantly higher than the IVF group after 3-year follow-up (ICSI boys: 8.62%, IVF boys: 5.21% [p < 0.05]), even though there was no significant difference at birth. Compared with IVF, FET may not increase risk of birth defects. Children conceived through ICSI, especially males, had higher rates of congenital malformations that were inapparent at birth. So longitudinal monitoring may provide insights into the risks of ART.

Can we improve obstetric outcomes in type 1 diabetic pregnancy?

The 2002-3 national survey of diabetic pregnancy (CEMACH)1 confirmed the continued poor outcomes in diabetic pregnancy.Pregnancies in a consecutive cohort of 197 type 1 diabetic women who reached the second...

Effects of fried potato chip supplementation on mouse pregnancy and fetal development

Objective Acrylamide (ACR), a proven rodent carcinogen, is present at significantly high quantities in commonly consumed foods such as potato chips, raising a health concern worldwide. Methods The effects of ACR and fried potato chips (FPC) on pregnant mice and their offspring before and after birth were investigated and compared. Results In the pregnant mice, similar histologic abnormalities were found in various tissues for ACR intoxication and FPC supplementation. Drastic alterations were mainly seen in the liver, kidney, heart muscle, and epiphyseal cartilage of experimental dams. ACR and FPC increased the rate of abortion and neonatal mortality and decreased the total number, body weight, size, and crown–rump length of the offspring before and after birth. Interestingly, however, higher rates of congenital malformations were observed in the FPC-treated group. Although ossification of axial and appendicular bones was markedly retarded during fetal development, some ossified bones were missing in newly born offspring of treated groups. Furthermore, the incidence of missing ossification centers was higher in the FPC-treated than in the ACR-treated neonates. Conclusion These results suggest that FPC can cause hazardous health effects and warrant a systematic study on the health effects of consumption of FPC and French fries in the general population.

International Perspectives

Regionalized level III perinatal care was implemented in Poland in 1998, but no comparative analyses of neonatal mortality and morbidity between other European regions and Poland are yet available. Given the large differences in policy and organization of health care between European countries, studying clinical outcomes within this context provides an opportunity to explore the effectiveness of regionalized care. The aim of this analysis was to compare the specific position of neonatal care in Poland with that of other European regions participating in the Models of OrganiSing Access to Intensive Care for very preterm babies (MOSAIC) project. In 1988, there were 18,798 live births in the 11 neonatal units in the Wielkopolska region; in 2003, there were 42,619 live births in the MOSAIC program from 53 neonatal units in the Wielkopolska and Lubuskie regions. There was no change in the rate of very preterm live births between 1988 and 2003, but the mortality rate among infants between 27 and 31 weeks of gestation differed significantly. The in-hospital mortality rate in the two Polish regions was higher in 2003 compared with other MOSAIC participants (35.3%and 17.3%, respectively). There was also a higher rate of congenital malformations, intraventricular hemorrhage, and periventricular leukomalacia. There were also clear differences in organization of perinatal care, with fewer level III centers per 10,000 deliveries in Polish regions compared with other European regions (0.25 and 1.33, respectively) and longer distances of neonatal transport (97 km and 29 km, respectively).

Parameters Associated With Outcome in Third Trimester Monochorionic Diamniotic Twin Pregnancies

ObjectiveTo assess parameters associated with perinatal and neonatal morbidity and mortality in monochorionic (MC) diamniotic twin pregnancies after 25 weeks of gestation. MethodsNeonatal outcomes after 25 weeks' gestational age were retrieved for all twin pregnancies between the years 2001 and 2007 and documented according to chorionicity. The features of MC pregnancies that resulted in intrauterine or neonatal demise were reviewed carefully to find an explanation for the adverse outcome. ResultsThe features of 93 pairs of MC twins were recorded and compared with those of 428 consecutive pairs of dichorionic (DC) twins. Perinatal mortality was higher in the MC twin pregnancies (1.61% vs. 0.35%, P= 0.04). Average gestational age at delivery (34.8 vs. 35.9 weeks, P< 0.001), mean birth weight (2127g vs. 2443 g, P< 0.001), and birth-weight adjustment for gestational age were all lower in the MC twin group than in the DC group. Severe discordant growth of the twins (>20% difference in birth weights) was significantly more common in MC pregnancies (25.81% vs. 11.68%, P< 0.001). After excluding cases of discordant growth, gestational age at delivery was not significantly different between the two groups. MC twins were more likely to have lower Apgar scores (8.5 vs. 8.9 at 5 minutes, P= 0.007), a higher rate of congenital malformations (13.98% vs. 8.18%, P= 0.01), higher rates of admission to the NICU (55.91% vs. 36.57%, P< 0.001), and higher rates of velamentous cord insertion (8.60% vs. 4.56%, P< 0.001). ConclusionEven in the presence of apparently normal progress, MC twin pregnancies should be monitored frequently throughout pregnancy, including during the third trimester.

Intrauterine fetal death after multiple umbilical cord torsion—complication of a twin pregnancy following assisted reproduction

Patients requiring assisted reproductive techniques may have a higher rate of congenital malformations. Some rare complications of pregnancy might be related to such abnormalities. Torsions of the umbilical cord resulting in fetal death have previously been described exclusively in pregnancies following spontaneous conception. The case of 37 year old gravida I, para O woman with a twin pregnancy after intracytoplasmatic sperm injection and intrauterine death of one twin at approximately 30 weeks' gestation is presented. The surviving twin was delivered by cesarean section at 31 weeks after spontaneous onset of labor and recurrent fetal bradycardia. The intraoperative situs showed that the demised twin had suffered from multiple umbilical cord torsions leading to intrauterine hypoperfusion. Umbilical torsion leading to fetal death might represent a previously unrecognized complication in women requiring assisted reproductive techniques, but this problem is known to occur in pregnancies achieved by natural methods.

Bifid tongue: A rare feature associated with infants of diabetic mother syndrome

Infants born to diabetic mothers (IDM) are well documented to have a higher rate of congenital malformations. Sacral agenesis/hypogenesis and caudal dysgenesis are classically linked to maternal diabetes, but many other types of anomalies are more frequent. In this case report, we describe a male infant born to a diabetic mother who in addition to other typical congenital abnormalities was born with an impressive bifid tongue. Accompanying congenital anomalies include unilateral microphthalmia, bilateral microtia, cleft palate, micropenis with unilateral cryptorchidism, bilateral radial hypoplasia, unilateral pre-axial polydactyly, and mid-line central nervous system defects including arhinencephaly and pituitary hypoplasia. Review of the literature reveals an additional case of an infant with a bifid tongue born to a diabetic mother [Comess et al., 1969]. In conclusion, bifid tongue without oral hamartoma, a rare congenital anomaly, can be an associated finding in IDM.

Effect of maternal congenital heart defects on labor and delivery outcome: A population-based study

Objective. The primary objective of this study was to characterize the delivery outcome of parturients with congenital heart defects (CHD), from maternal and from neonatal perspectives.Study design. A retrospective population-based study was conducted, covering a 13-year period (1989–2002) with an aggregate of 151 487 deliveries of all women with and without CHD. Maternal demographics, obstetrical and medical history, delivery outcome, and neonatal outcome were drawn from a computerized perinatal database.Results. Sixty-seven women with CHD had 156 deliveries. The severity of CHD, based on the New York Heart Association (NYHA) classification, was I or II in 99.1% of the deliveries. CHD patients had significantly higher rates of labor induction and neonatal malformations. Maternal CHD was discovered as an independent risk factor associated with neonatal malformations (OR 2.10, 95% CI 1.18–3.72). No significant differences were noted between women with CHD and the controls regarding maternal morbidities and Apgar scores.Conclusions. The labor outcome of CHD patients with NYHA classification I and II resembles that of non-CHD women in a tertiary center setting. Neonates of CHD mothers have higher rates of congenital malformations even among asymptomatic or mildly symptomatic mothers. A careful sonographic follow-up is warranted among all pregnancies of CHD patients.

Pregnancy and perinatal outcome in epileptic women: A population-based study

Objective. To investigate the pregnancy outcome of patients with epilepsy.Study design. A population-based study comparing all singleton pregnancies of patients with and without epilepsy was performed. Patients lacking prenatal care were excluded from the analysis. Deliveries occurred between the years 1988 and 2002 in a tertiary medical center. Stratified analysis, using a multiple logistic regression model, was performed to control for confounders.Results. During the study period 139 168 singleton deliveries occurred in our medical center. Of these, 220 (0.2%) were of patients with epilepsy. With the exception of gestational diabetes mellitus (GDM), no other significant differences regarding maternal outcomes were noted between the groups. However, a higher rate of congenital malformations was noted among the epileptic population (7.7% vs. 3.8%; p < 0.001). Also, a higher rate of cesarean deliveries (CD) was found among epileptic women (17.3% vs. 11.55%, p = 0.008). This association was persistent after controlling for possible confounders, using a multivariable analysis (OR = 1.5, 95% CI 1.1–2.3; p = 0.05).Conclusion. The course of pregnancy of patients with epilepsy is favorable, except for higher rates of cesarean deliveries, GDM, and congenital malformations.

Pregnancy Outcome and Clomiphene Citrate Dose.

Background: Clomiphene citrate (CC) has been shown to result in isomer-specific systemic accumulation of zuclomiphene across consecutive cycles of ovulation induction. Due to prolonged nuclear receptor occupancy and anti-estrogenic activity, it is biologically plausible that CC may influence early embryonic development and lead to higher rates of congenital malformations and spontaneous abortions. Furthermore, there is a paucity of data with respect to adverse reproductive outcome following CC treatment in doses up to 250 mg/day.

Differences in preterm delivery rates and outcomes in Jews and Bedouins in southern Israel

Objective: (1) To compare the preterm delivery rates in the Bedouin versus the Jewish population. (2) To compare risk factors for preterm delivery in the two populations. (3) To compare outcomes of preterm delivery between the two groups. Study design: 41 669 Jewish singletons births of whom 2816 delivered preterm (23–36 weeks) and 26 495 Bedouin singletons in whom 2064 preterm deliveries occurred, were compared. All births took place in Soroka University Medical Center. Data were obtained from the computerized database of birth discharge records. Results: The incidence of preterm delivery in Bedouin women was significantly higher than the rate in Jewish women (7.8 vs. 6.8%, P<0.01). The grand multiparity rate was higher among Bedouin women ( P<0.001), as was the rate of teenage (<19 years) mothers ( P<0.001). Gestational diabetes, PIH, and PROM rates were higher in the Jewish population ( P<0.001, P=0.017, P<0.001, respectively). A bad obstetric history and previous perinatal mortality is more common in the Bedouin population ( P<0.001 for both). In a logistic regression model including all these factors, the ethnic difference in the incidence of preterm delivery remained significant. The neonatal mortality rate was higher in the Bedouin population ( P<0.001), as was the rate of congenital malformations ( P<0.001). The perinatal mortality of Bedouins was nearly twice that of Jewish neonates with congenital malformations. However, no difference was found when neonates without congenital malformations were compared. Congenital malformations were found to be the strongest predictor of mortality. Ethnicity per se was no longer a predictor of mortality once congenital malformations were included in a logistic regression model, but the interaction of Bedouin ethnicity and congenital malformation was a significant predictor of mortality. Conclusion: The incidence of preterm delivery was significantly higher in Bedouin women than in Jewish women. A full explanation for this difference was not found. However, there were significantly higher rates of congenital malformations in the Bedouin preterm delivered infants. There was a much higher rate of neonatal mortality in the Bedouin population and this ethnic difference was fully explained by the presence of congenital anomalies.

Hyperglycemia induces apoptosis in pre-implantation embryos through cell death effector pathways.

Although perinatal mortality rates have improved for pregnant diabetic women because of insulin therapy and tight metabolic control, infants of diabetics still experience significantly higher rates of congenital malformations and spontaneous miscarriages compared with those of non-diabetic women. Our results here indicate that hyperglycemic conditions, either in vivo or in vitro, modulate the expression of an apoptosis regulatory gene as early as the pre-implantation blastocyst stage in the mouse. Apoptosis in the mammalian pre-implantation blastocyst is a normal process, thought to protect the early embryo by eliminating abnormal cells. Here we demonstrate that expression of Bax, a Bcl-2-like protein, is increased at the blastocyst stage in the presence of high concentrations of glucose, and that these changes correlate morphologically with increased DNA fragmentation. Expression of Bax and caspase are necessary for this in vitro glucose-induced apoptotic event, and ceramide is involved in mediating this embryotoxic effect of glucose. We also show that these apoptotic cellular changes can be prevented in vivo by treating hyperglycemic mice with insulin before and immediately after conception. These findings emphasize the importance of tight glycemic control in diabetic women at the earliest stages after conception.

Combing Diabetes' Teratogenic 'Suspect List'

ABSTRACT INFANTS of insulin-dependent diabetic mothers have a twofold to threefold higher rate of congenital malformations than infants of mothers without the disorder. In recent years, blood glucose has topped the list of teratogenic suspects, so much so that a recent controversial study suggested that slightly elevated levels even in nondiabetic mothers were associated with an increased incidence of congenital abnormalities in their offspring (N Engl J Med 1986;315:989-992). However, the inclusion of anomalies not typically associated with diabetic pregnancies raised questions about the study's conclusions (N Engl J Med 1987;316:1343-1346).Now, data from the Diabetes in Early Pregnancy Study, one of the largest ever to follow diabetic women throughout their pregnancies, suggest that while glucose control plays a role in malformations, investigators must redouble their search for other factors if they hope to prevent problems such as caudal regression (sacral dysgenesis and hypoplasia of the femora) and congenital heart defects