Pregnancy outcome following maternal exposure to statins: a multicentre prospective study.

OBJECTIVE: This contribution addresses the risk associated with exposure to statins during pregnancy. DESIGN: Multicentre observational prospective controlled study. SETTING: European Network of Teratology Information Services. POPULATION: Pregnant women who contacted one of 11 participating centres, seeking advice about exposure to statins during pregnancy, or to agents known to be nonteratogenic. METHODS: Pregnancies exposed during first trimester to statins were followed up prospectively, and their outcomes were compared with a matched control group. MAIN OUTCOME MEASURES: Rates of major birth defects, live births, miscarriages, elective terminations, preterm deliveries and gestational age and birthweight at delivery. RESULTS: We collected observations from 249 exposed pregnancies and 249 controls. The difference in the rate of major birth defects between the statin-exposed and the control groups was small and statistically nonsignificant (4.1% versus 2.7% odds ratio [OR] 1.5; 95% confidence interval [95% CI] 0.5-4.5, P = 0.43). In an adjusted Cox model, the difference between miscarriage rates was also small and not significant (hazard ratio 1.36, 95% CI 0.63-2.93, P = 0.43). Premature birth was more frequent in exposed pregnancies (16.1% versus 8.5%; OR 2.1, 95% CI 1.1-3.8, P = 0.019). Nonetheless, median gestational age at birth (39 weeks, interquartile range [IQR] 37-40 versus 39 weeks, IQR 38-40, P = 0.27) and birth weight (3280 g, IQR 2835-3590 versus 3250 g, IQR 2880-3630, P = 0.95) did not differ between exposed and non-exposed pregnancies. CONCLUSIONS: This study did not detect a teratogenic effect of statins. Its statistical power remains insufficient to challenge current recommendations of treatment discontinuation during pregnancy.

Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus.

Despite publication of guidelines for the prevention and management of hyperbilirubinemia in term and late-preterm newborn infants, kernicterus, although rare, continues to occur. Guidelines written for use in one country may not always be universally appropriate. Bearing this in mind, a committee appointed by the Israel Neonatal Society has formulated a set of guidelines, based on those of the American Academy of Pediatrics (2004), but adapted to the realities of the Israeli scene. The guidelines include methods of surveillance of jaundice, prediction of jaundice, assessment of risk factors, discharge planning and post-discharge follow-up, in addition to therapeutic guidelines including indications for phototherapy, exchange transfusion and the use of intravenous immune globulin. Availability of these guidelines to the international community may offer direction to physicians of other countries who may be setting up guidelines for use in their own communities.

Mortality of full-term infants during the first month of life in a tertiary care hospital.

OBJECTIVE: The neonatal mortality rate is disproportionately influenced by preterm infants and does not reflect the rate in full-term infants. Our objectives were to estimate the full-term neonatal mortality rate and to identify causes of death in full-term infants during the first month of life. STUDY DESIGN: A retrospective study of full-term infant deaths during a 6-year period from 2000 to 2005, in a tertiary medical center. RESULT: During the study period there were 44,703 full-term births and 31 deaths, representing a mortality rate of 0.69 per 1,000 live births. The main cause of death was congenital anomalies (64.5%), specifically cardiac anomalies. Other causes were chromosomal anomalies or syndromes (12.9%), labor complications (12.9%), infections (3.2%), congenital diseases (3.2%) and metabolic disorders (3.2%). CONCLUSION: The mortality rate of full-term infants may be lower than previous estimates. Efforts aimed at decreasing mortality among full-term infants should focus on prenatal diagnosis.

Gestational diabetes mellitus. A survey of perinatal complications in the 1980s.

Neonatal morbidity was assessed in the offspring of 878 mothers with gestational diabetes mellitus (GDM), 132 mothers with pre-GDM, and 380 control subjects. Compared with the control group, the GDM group had a higher incidence of complications, including macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, polycythemia, and major congenital anomalies (P less than 0.05). Although our GDM patients were stringently managed with diet or diet plus insulin, as indicated, and maintained almost euglycemic values, these neonatal complications could not be eliminated. Our data may be consistent with observations published during the last decade that even subtle degrees of maternal hyperglycemia can have a detrimental effect on perinatal outcome. Most neonatal complications readily respond to therapy if diagnosed and treated early and promptly. Macrosomia can have a detrimental effect on delivery (trauma) and later long-term implications during childhood. Tight metabolic control with diet and, when indicated, insulin treatment may be advantageous in reducing fetal birth weight. Criteria of how tight the metabolic control should be remain to be accurately defined.

The effect of gestational age on neonatal outcome in low-risk singleton term deliveries.

OBJECTIVE: To assess the association between gestational age at delivery and adverse neonatal outcome among term low-risk singleton neonates. METHODS: A retrospective cohort study design was used. The study group included all low-risk singleton term (37 + 0 to 41 + 6 weeks) newborns delivered in a single tertiary university-affiliated medical center over a 5-year period. Outcome of neonates delivered at 37 + 0 to 37 + 6 weeks of gestation (early term) and 41 + 0 to 41 + 6 weeks of gestation (late term) was compared to that of neonates delivered at 39 + 0-39 + 6 weeks of gestation (control). RESULTS: Overall, the outcome of 30 229 neonates was analyzed. The incidence of neonatal mortality was 1.0 per 1000 live-born neonates, with no significant difference between the various gestational age groups. Early term newborns were at higher risk for respiratory morbidity, hypoglycemia, hypocalcemia, thrombocytopenia and unexplained jaundice, and had higher rates of prolonged hospital stay, NICU admission, sepsis workup and antibiotic treatment. On multivariate analysis, early term delivery was an independent predictor for composite respiratory morbidity (OR=2.4, 95% CI 1.6-3.8, p < 0.001), unexplained jaundice (OR=2.1, 95% CI 1.7-2.5, p < 0.001), hypoglycemia (OR=2.5, 95% CI 1.5-4.3, p < 0.001) and NICU admission (OR=1.9, 95% CI 1.5-2.5, p < 0.001). Late term neonates had a significantly higher rate of large for gestational date, but did not differ from controls with respect to the rate of composite neurologic or respiratory complications, NICU admission, birth trauma or infectious morbidity. CONCLUSION: Even in low-risk singleton deliveries, early term is associated with an increased risk of neonatal morbidity.

A possible role for aspartic acid in neonatal seizures.

Aspartic acid concentration in CSF was markedly elevated in a newborn infant with severe, intractable seizures. The levels of all other amino acids in blood, urine, and CSF were within the normal range. Two of the six other siblings in this consanguineous family died in early infancy of a similar condition. Since aspartic acid is a putative excitatory neurotransmitter, a possible causal relationship is suggested between its increased CSF concentration and the occurrence of neonatal convulsions in this family.

Neonatal polycythemia: I. Early diagnosis and incidence relating to time of sampling.

The dynamic changes occurring in hematocrit and blood viscosity within the first 18 hours of life were studied in 50 full-term infants who were vaginally delivered and had weight appropriate for gestational age. In all cases, the cord was clamped within 30 seconds and cord blood was collected from the vein and artery. Subsequently, samples were taken from a peripheral vein at ages 15 minutes, and 2, 4, 6, and between 12 to 18 hours. Both the Hct and blood viscosity reach their peak at age 2 hours. The incidence of neonatal polycythemia varied greatly with age. Thus at the age of 2 hours, ten infants (20%) were polycythemic, whereas by age 6 hours only six (12%) of these infants were still polycythemic and by age 12 to 18 hours only one infant (2%) was polycythemic. A linear correlation was found between cord Hct levels and peripheral venous Hct levels by age 2 hours. None of the infants with cord blood Hct levels less than or equal to 56% had developed polycythemia, whereas ten of the 12 infants with cord Hct levels greater than 56% developed polycythemia. In this particular group of infants, cord blood Hct levels may be used for the screening of neonatal polycythemia.

Sternum length, torso length, and internipple distance in newborn infants.

In order to define standards for sternal length, torso length, and internipple distance in the newborn infant, 198 term and preterm infants (27 to 41 gestational weeks) were examined. In every case, the gestational age was determined chronologically and clinically. Sternal and torso length and internipple distance were measured by two observers using standard measurement techniques. Normal values are presented by plotting the mean +/-2 SD for each gestational week v the gestational age.

Neonatal polycythemia: II. Definition related to time of sampling.

The mathematical relationship between blood viscosity and hematocrit levels was studied in 93 venous blood samples drawn within the first 6 hours of life from 20 full-term infants with weight appropriate for gestational age. A highly significant linear correlation (r = .948) between the logarithm of the viscosity at all the shear rates examined and the Hct was found. This indicates an exponential relationship between the blood viscosity and the Hct levels for every value of the Hct greater than 42%. A new dynamic definition of neonatal polycythemia, which takes into consideration the time of sampling, is suggested. By determining the mean + 2 SD, the upper limit of the normal Hct at the age of 2 hours was 71% and at the age of 6 hours was 68%.

Determination of anterior displacement of the anus in newborn infants and children.

Anterior displacement of the anus is a common cause of constipation in infancy and early childhood. However, normal values are not available for defining anal displacement. Using a simple technique, an anal position index of less than 0.34 in girls and less than 0.46 in boys was indicative of anterior displacement. The diagnosis can be made in the neonatal period.

Neonatal pemphigus vulgaris.

The case history of a baby with neonatal pemphigus vulgaris is presented. This is the 13th case of pemphigus vulgaris during pregnancy reported in the literature. The correlations between the clinical, histologic, and immunofluorescent findings are discussed and a review of all previously reported cases is presented.

Skin barrier properties in different body areas in neonates.

OBJECTIVE: The aim of the study was to investigate skin barrier function in neonates in different anatomic sites during the first 2 days of life. DESIGN: The study population consisted of 44 healthy full-term newborn infants. Transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH were measured in different anatomic sites (forehead, flexor part of forearm, upper back, abdomen, inguinal region, palms, and soles) during the first 10 hours of life and 24 hours later. Measurements were recorded with a Tevameter, a Corneometer, and a skin pH meter with a flat glass electrode. Results were compared with those in 20 healthy adults. RESULTS: TEWL was lower in infants than in adults in the forehead, palms, soles, and higher in the forearms. It was significantly higher on day 1 than on day 2 in the soles, palms, and forearms, and in the forearm, palms, and inguinal region compared with the other anatomic sites. SCH was significantly lower in the infants on the forehead, back, and abdomen, and higher on the forearms and palms; it was significantly higher on the first day of life on the forearms and palms, and lower in the inguinal region. Skin surface pH was significantly higher in the infants in all body sites (>6.6 in most measurements). On day 2, it was significantly lower than on day 1, but still higher than in adults. SCH correlated positively with TEWL in the neonates but not in the adults. None of the variables were related to gestational age, sex, mode of delivery, or body weight. CONCLUSIONS: Changes take place in SCH, water loss, and pH in the first 2 days after birth, suggesting that the stratum corneum barrier is still in the process of adapting to extrauterine life. The significant anatomic variability in TEWL and SCH should be taken into account in evaluating the permeation of skin care products and topical medications in newborns.

The effect of light on oxygen-induced vasoproliferative retinopathy in newborn kittens.

The effect of bright fluorescent light (115 fc) on oxygen-induced retinopathy in newborn kittens was compared with that of complete darkness and cyclic illumination of 12 hr of bright light (115 fc) and 12 hr of complete darkness. No significant difference was found in the extent of preretinal vasoproliferation and retinal ultrastructural findings among the three groups of kittens reared in different levels of illumination and a control group raised in a standard laboratory illumination level of 40 fc. These results confirmed that light is not a required factor for the development of oxygen-induced retinopathy in kittens.

Adams-Oliver syndrome: autosomal recessive inheritance and new phenotypic-anthropometric findings.

We describe a new family with Adams-Oliver syndrome. One sib had scalp aplasia cutis congenita (SACC) and cutis marmorata and a second sib had SACC, cutis marmorata, and terminal lower limb defects. In both the findings were associated with oligohydramnios. The pedigree suggests autosomal recessive inheritance. New phenotypic-anthropometric findings in one infant were upper limb micromelia and brachypodia.

Congenital anomalies concomitant with persistent primary congenital hypothyroidism.

The Israeli national neonatal screening program for congenital hypothyroidism (CH) was initiated in May 1978. The overall incidence of persistent primary congenital hypothyroidism (PPCH) during the first 10 years of screening was 1:2,950 live births. The purpose of this study was to ascertain the incidence of congenital extrathyroid anomalies (ETAs) among the infants with PPCH and to compare it with the Israeli Birth Defect Monitoring System data. Among 243 PPCH infants on whom adequate data were available, 38 infants (15.6%) had associated congenital anomalies. Fourteen infants had congenital cardiac anomalies (5.8%): VSD (n = 7), PDA (n = 3), PS (n = 2), one mitral insufficiency, and one congenital atrial flutter. Eight children (3.3%) had congenital dislocation of the hip; their M:F ratio was 3:5 similar to the M:F ratio in CH (unlike the ratio in the general population). Some additional anomalies were considerably more common than in the general population. It is reasonable to assume that teratogenic effects active during organogenesis may affect simultaneously many organs, including the developing thyroid, causing a relatively high percentage of CH infants with congenital ETA.

Autosomal dominant cerebro-costo-mandibular syndrome: ultrasonographic and clinical findings.

We describe two patients, a father and his daughter, with the cerebro-costo-mandibular syndrome. New manifestations not previously described include microstomia, long philtrum, posterior cervical skin fold, short internipple distance, and depressed sacral region. The presence of hydrocephaly in the proposita and spina bifida in the father may be other manifestations of neuraxial involvement in this syndrome. The first intrauterine ultrasonographic documentation of this syndrome showed polyhydramnios and, especially, the very unusual shape of the ribs, which were short and defective. Most characteristics of the pedigree point to autosomal dominant inheritance. The great variability of inheritance and expressivity of the very few documented familial cases described in the literature, together with the great frequency of sporadic cases, indicates genetic heterogeneity of this syndrome.

Normal pulmonary function in a monoamniotic twin discordant for bilateral renal agenesis: report and review.

Renal agenesis and obstructive urinary tract anomalies causing oligohydramnios usually result in pulmonary hypoplasia. We report on the first female monoamniotic twin born with a combination of bilateral renal agenesis, agenesis of the urinary collecting system, absent external genitalia, anal atresia and single umbilical artery, compatible with VATER association but with normal pulmonary function. The infant had none of the manifestations of Potter sequence, in particular the facial changes and pulmonary hypoplasia typically associated with bilateral renal a/dysgenesis. The monoamniotic cotwin had normal renal function, such that sufficient amniotic fluid volume was maintained. This patient emphasizes the importance of adequate amniotic fluid volume for normal pulmonary development. The possible underestimation of genital malformations in the VATER association should be considered. Also noteworthy is the rare absence of external genitalia.

Marked parental consanguinity as a cause for increased major malformations in an Israeli Arab community.

It is common among Israeli Arabs who live in the villages to prefer consanguineous marriages, particularly among first cousins. In addition, such villages are populated by a few (less than 20) original families, and inter-family/inter-village marriages are infrequent. The purpose of this study was to examine the consequences of such "consanguinity" in Taibe, a large Arab village, 30 km from Tel Aviv. Six hundred ten families were prospectively ascertained through infants who were routinely seen in the local "Well Baby Clinics." A significant increase in the incidence of major malformations was noted in relation to the closeness of the parental relationship. For the index cases group the prevalence of individuals with major malformations were 5.8% in the product of inter-village marriages, 8.3% in the intra-village non-related matings, 15.1% in the distant consanguineous group, and up to 15.8% in the progeny of first-cousin marriages (P less than 0.001). In the siblings of these index cases, the frequency of major malformations was 4.3%, 4.5%, 10.5%, and 10.3%, respectively. Analysis of the major malformations by each body system showed the same trend. The study demonstrates a marked high rate of consanguineous marriages, whose effect leads to a marked increase in major malformations and thus a prominent public health problem in such villages. This requires a unique genetic counseling approach.

Decreased developmental stability as assessed by fluctuating asymmetry of morphometric traits in preterm infants.

Fluctuating asymmetry (FA) of 8 morphometric traits was studied in 113 preterm infants (26-36 wk of gestation), 103 term infants (37-41 wk), and their respective parents. With 3 different measures of FA, the highest values were obtained from extremely preterm infants (26-29 wk), and the lowest from the group of term infants. The estimates of FA values among parents, particularly mothers, showed a similar, albeit less pronounced, trend. Multiple regression analysis of individual mean FA values, calculated in infants for the 8 studied bilateral traits, documented a significant inverse correlation with gestational age and with the health status of the infants and their mothers, as well as a positive correlation with the mothers' mean FA values.