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.

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.

Long-term outcome following selective serotonin reuptake inhibitor induced neonatal abstinence syndrome.

OBJECTIVE: To assess the long-term neurodevelopment of children exposed in utero to selective serotonin reuptake inhibitors (SSRIs) that developed a neonatal abstinence syndrome (NAS). STUDY DESIGN: Neurodevelopmental evaluation was performed at the age of 2 to 6 years. Children who developed NAS were compared with those who did not using univariate and logistic regression analyses. RESULT: Thirty children with NAS and 52 without NAS participated in the study. Both groups were similar in mean cognitive ability (106.9±14.0 vs 100.5±14.6, P=0.12) and developmental scores (98.9±11.4 vs 95.7±9.9, P=0.21). However, there was a trend towards small head circumference in the NAS group (20 vs 6%, P=0.068). NAS was associated with an increased risk of social-behavior abnormalities (odds ratio (OR) 3.03, 95% confidence interval (CI) 1.07 to 8.60, P=0.04) and advanced maternal age (OR 1.12, 95% CI 1.00 to 1.25, P=0.04). CONCLUSION: Infants who developed NAS had normal cognitive ability, but were at an increased risk for social-behavioral abnormalities. Follow-up evaluation of symptomatic neonates should be considered.

Anthropometric indices at age 17 years of full-term neonates born short.

BACKGROUND: Measurements at the end of puberty of neonates short for gestational age (SGA-L) are scant. OBJECTIVE: To determine the correlation between birth length and weight in neonates, with height and weight at age 17 years. SUBJECTS AND METHODS: 385 full-term neonates, measuring less than 48 cm (SGA-L) and 585 full-term neonates, measuring 48 cm or greater (adequate birth length for gestational age; AGA-L) were included. 234 SGA-L and 359 AGA-L were identified at age 17 years. RESULTS: Comparison of the two groups revealed that both sexes born SGA-L were also shorter at age 17 years than those born AGA-L (girls 158.9 cm (SD 7.6) vs 164.2 cm (SD 64) (p<0.001) and boys 167.3 cm (SD 8.7) vs 173.8 cm (SD 7.1) (p<0.001)). The subjects born SGA-L also weighed significantly less than those born AGA-L (p<0.001) both at birth and at age 17 years. CONCLUSIONS: Children born SGA-L become short adults and weigh less at age 17 years than children with a normal birth length.

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.

Leptin, insulin, insulin-like growth factors and their binding proteins in cord serum: insight into fetal growth and discordancy.

OBJECTIVE: Singleton infants with intrauterine growth restriction have an adaptive hormonal profile characterized by decreased levels of IGF-1, IGF-2, IGFBP-3 and insulin and elevated levels of IGFBP-1 and IGFBP-2. This study examined the association between cord serum levels of six growth factors and anthropometric features at birth in twins in order to determine the intrauterine growth factor interactions and to characterize the specific hormonal profile of small discordant twins. DESIGN: Prevalent case-control study. PATIENTS: Twenty pairs of discordant twins (5 monozygotic, 15 dizygotic) and 20 pairs of concordant twins (6 monozygotic, 14 dizygotic) matched for gestational age. MEASUREMENTS: Cord blood levels of IGF-1, IGF-2, IGFBP-1, IGFBP-3, insulin, leptin and anthropometric measurements at birth. Intra- and inter-pair differences and correlation coefficients were calculated, and the data were fitted to multivariate regression models. RESULTS: In both discordant and concordant groups, the smaller twins had a significantly lower level of IGF-1 (P < 0.03) and significantly higher level of IGFBP-1 (P < 0.02) than their larger cotwins. IGFBP-1 was inversely correlated with IGF-1 (P < 0.05). Insulin levels were significantly higher in the smaller discordant than the smaller concordant twins (P < 0.001) and in the larger discordant than the larger concordant twins (P < 0.004). Among the monozygotic twins, the leptin level was significantly higher in the larger discordant than the larger concordant twins (P < 0.025). Percentage birth weight discordancy was statistically correlated with twin-pair differences in IGF-1 and IGFBP-1. CONCLUSIONS: Of the six factors studied, IGF-1 appears to be the main indicator of intrauterine growth. Twin discordancy may involve compensatory rather than adaptive mechanisms or a multihormone relative resistance syndrome.

Prolonged QT interval in an infant of a fluoxetine treated mother.

Fluoxetine is an antidepressant drug, only recently discovered to be a QT interval prolonging agent. The first case is presented of an infant of a mother treated with fluoxetine during pregnancy who had a transiently prolonged QTc interval, concluded to be drug induced. Clinical and electrocardiographic monitoring of newborns of antidepressant treated mothers is needed.

Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma.

OBJECTIVE: To determine the prognostic value of sonographically detected fetal hyperechogenic kidneys with normal amniotic fluid volume. METHODS: Seven cases of hyperechogenic fetal kidneys were identified by sonography over a 7-year period (1996--2002). Increased renal echogenicity was diagnosed when the renal parenchyma was of greater echogenicity than adjacent liver tissue. Amniotic fluid volume was measured by the semiquantitative sonographic technique known as the amniotic fluid index (AFI). RESULTS: Three of the live-born infants had autosomal dominant polycystic kidney disease and one had autosomal recessive polycystic kidney. In the remainder, autopsy study revealed multifocal renal dysplasia in two cases and normal kidneys in one. CONCLUSIONS: Increased renal echogenicity with normal amniotic fluid volume in a fetus without other anomalies is a difficult diagnostic dilemma. Although it is usually indicative of renal parenchymal disease with possible renal failure after birth or in early childhood, in some cases, it represents a normal variant. .

Congenital malformations and developmental changes of the breast: a neonatological view.

Congenital malformations of the breast and nipple-areolar complex are described from the aspect of neonatal dysmorphology. Their classification is based on the accepted nomenclature in the medical literature and on a special method of clinical examination. The embryology and the possible genes involved in breast development are also discussed to clarify the mechanisms underlying the occurrence of breast malformations. Except for amastia, polymastia and polythelia, which have received much attention, the data for many other breast malformations are sparse. Case control studies or even case series are rare, and good evidence is often lacking. In addition, more studies are needed to complete the map of genes involved in breast development. This information will contribute substantially to our understanding and clinical approach to breast malformations in the future.

Neurobehavioral and autonomic effects of hammock positioning in infants with very low birth weight.

PURPOSE: This study was designed to determine whether supine positioning of infants born preterm in a hammock instead of the prone position affects their neuromuscular maturity, growth, and autonomic stability. METHODS: Twenty healthy infants who were born premature with very low birth weight (VLBW) (<1500 g) were randomized into two groups. Subjects were pair-matched for weight (difference less than 100 g), gestational age (difference less than eight days), and postnatal age (difference less than eight days). Ten infants were placed supine in a hammock for three hours daily for ten consecutive days, and ten infants were maintained nested in the prone position. Neuromuscular maturity (based on three neurological parameters adopted from the Ballard examination), heart rate, respiratory rate, and weight gain (g/cal) were compared between the groups. RESULTS: Compared with nested prone positioning, supine positioning in a hammock was associated with a higher neuromuscular maturity score (p < 0.003) and a more relaxed condition, as expressed by lower heart rate and respiratory rate (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: Maintaining infants who were born preterm with VLBW in the supine position in a hammock may positively affect their autonomic stability and neuromuscular maturity.

Sore Throat Treatment during Pregnancy : A Prospective, Controlled, Pilot Study.

OBJECTIVE: To determine whether exposure during pregnancy to two types of lozenges used for treatment of sore throat [Kalgaron® (Rafa Laboratories, Jerusalem, Israel) or Strepsils® (Boots Healthcare International, Nottingham, UK)] was associated with an increased risk of malformations, spontaneous abortions or decreased birthweight. DESIGN: Prospective, controlled, observational study. STUDY PARTICIPANTS: The study group included 54 women who received Kalgaron® or Strepsils® during the first trimester of pregnancy. The control group included 54 women exposed to non-teratogenic drugs. RESULTS: The rate of major malformations in the study group (3.84%) did not differ from that of the control group (3.92%) [p = 0.98; relative risk 0.98, 95% confidence interval 0.14 to 6.7]. The rate of minor malformations in the study group (1.92%) did not differ statistically from that of the control group (0%) [p = 0.32]. There were also no statistically significant differences in birthweight, rate of live births and rate of spontaneous abortions among the two groups. CONCLUSIONS: The use of Kalgaron® or Strepsils® during pregnancy was not associated with an increased risk of malformations, spontaneous abortions or decreased birthweight. However, larger studies are needed to confirm the safety of these medications during pregnancy.

Are singleton assisted reproductive technology pregnancies at risk of prematurity?

PURPOSE: Our purpose was to determine the risk of premature delivery among singleton pregnancies derived from assisted reproduction technology (ART). METHODS: Ninety-five singleton ART pregnancies and 190 matched spontaneous pregnancies were assessed for preterm delivery rates, pregnancy complications, and cesarean section rates in a retrospective study at an academic medical center. RESULTS: Among the ART singleton deliveries group (n = 95), 19 (20%) were preterm, which was statistically significantly higher than the 4% (8 of 190) found in the control group. Among the pregnancies achieved by intracytoplasmic sperm injection (ICSI) in the severe male-factor infertility subgroup (n = 22), only one preterm delivery occurred (4.5%). CONCLUSIONS: Singleton ART pregnancies are at an increased risk of preterm delivery compared to singleton pregnancies after spontaneous conception. The higher rate may be attributed to various infertility cofactors, such as uterine malformations, previous operative procedures that involved cervical dilatation, and a history of pelvic infection. This is supported by the finding that ICSI-derived pregnancies in couples with strict male-factor infertility are not at an increased risk of preterm delivery.

Cutis marmorata telangiectatica congenita and hypospadias: report of 4 cases.

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic congenital vascular anomaly. Of the 111 patients with CMTC examined in our clinic during the past 25 years, 4 were found to have hypospadias. All cases were sporadic. Although CMTC has been associated with various abnormalities, to our knowledge there are no reports in the literature of concurrent hypospadias.

Brachial plexus injury and obstetrical risk factors.

OBJECTIVE: To determine whether known historical risk factors of brachial plexus injury differ between affected neonates and healthy controls. METHODS: The files of all 62 children with Erb's palsy who were diagnosed after birth were reviewed. The control group consisted of 124 randomly selected uninjured infants born within the same period. RESULTS: Compared with the control group, the mothers of the neonates with brachial plexus injury were found to be significantly older (32.1+/-5.2 years vs. 28.9+/-5.8 years, P = 0.01), and had a significantly higher incidence of diabetic pregnancy (69% vs. 14.5%, P = 0.001); the infants had a significantly higher mean birth weight (3846+/-576 g vs. 3220+/-582 g, P = 0.0001) and higher incidence of birth weight > or = 4000 g (27% vs. 4.8%, P = 0.0001). Two of the infants in the study group (3.2%) were born by elective cesarean section. CONCLUSIONS: Brachial plexus injury is associated with several non-predictable or preventable risk factors.

On the symmetry of limb deficiencies among children with multiple congenital anomalies.

In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.

Insulin, insulin-like growth factors-I and -II and insulin-like growth factor binding protein-3 in newborn serum: association with normal fetal head growth and head circumference.

The insulin-like growth factors (IGF) and their binding proteins (IGFBP) have been implicated in the regulation of fetal weight and length. The aim of our study was to determine the relationship between head circumference at birth and serum levels of IGF-I, IGF-II, IGFBP-3 and insulin in full-term appropriate-for-gestational age (AGA) infants. Serum samples were obtained from 77 singleton full-term neonates, 69 AGA and 8 small-for-gestational age (SGA). The AGA infants were divided into three groups by head circumference: Group 1: < or = 3rd percentile; Group 2: at 50th percentile; Group 3: > or = 97th percentile. Serum levels of IGF-I, IGF-II, IGFBP-3 and insulin were determined with commercial kits and immunometric methods. There were no statistically significant differences in mean serum levels of IGF-I, IGF-II and IGFBP-3 between the groups. A significantly higher mean serum insulin level was noted in the AGA infants with a head circumference > or = 97th percentile compared to those with a head circumference < or = 3rd percentile (4.6 +/- 0.3 vs 3.3 +/- 0.6 microU/ml; p = 0.04), and in AGA infants with a head circumference above the 50th percentile compared to those with a head circumference below the 50th percentile (4.4 +/- 0.4 vs 3.3 +/- 0.3 microU/ml; p = 0.01). AGA infants with a head circumference above or below the 50th percentile did not differ statistically in their mean IGF-II and IGFBP-3 serum level, while IGF-I differed statistically between the groups (18 +/- 2.7 vs 11.6 +/- 1.6 ng/ml, respectively; p = 0.045). Using univariate analysis, head circumference correlated positively with insulin (r = 0.29; p = 0.016) and with IGF-I (r = 0.26; p = 0.03). A stepwise multivariate linear regression analysis, however, did show statistically significant correlation of head circumference with birth weight (f = 36; p = 0.0001), and only marginally with birth length (f = 4.7; p = 0.06) and insulin (f = 3.4; p = 0.07). No correlations were found between head circumference and IGF-I, IGF-II or IGFBP-3. These data suggest that apart from genetic and nutritional factors, insulin may play a role in promoting intrauterine head growth, as reflected by head circumference at birth.

Maternal anti-D prophylaxis during pregnancy does not cause neonatal haemolysis.

OBJECTIVE: To evaluate signs of haemolysis in babies of Rh-D negative mothers who underwent prophylaxis with anti-D immunoglobulin during pregnancy. DESIGN: The following were evaluated in all babies of Rh-D negative mothers born within a three month period in our department: haemoglobin level, packed cell volume, mean corpuscular volume, reticulocytes, bilirubin level, and direct Coombs' test (direct anti-globulin test). The babies were divided into two groups according to number of doses of anti-D immunoglobulin received by the mother (one or two), and then further divided by their Rh status (negative or positive). Findings were also compared with a control group of babies of O-Rh positive mothers. RESULTS: The study group consisted of 101 babies and the control group of 37 babies. No statistically significant differences were found for any of the haematological variables between the babies of mothers who received one or two doses of anti-D immunoglobulin, or between the Rh negative babies (n = 35), and the controls. Although 20% of the Rh positive babies born to mothers receiving two doses of anti-D immunoglobulin had a positive result in the direct Coombs' test compared with only 2.4% of the babies of mothers treated with only one dose, no signs of haemolysis were documented in the babies with a positive Coombs test. CONCLUSION: The prevention of Rh isoimmunisation with anti-D immunoglobulin (one or two doses) during pregnancy does not jeopardize the newborn. Blood group typing and direct Coombs' test should be performed in every newborn of an Rh negative mother to establish whether there is a necessity to administer anti-D. In the presence of a positive direct Coombs' test, the type of antibodies should be identified.