Neonatal intensive care admission for term neonates and subsequent childhood mortality: a retrospective linkage study.

BACKGROUND: Neonatal intensive care unit (NICU) admission among term neonates is a rare event. The aim of this study was to study the association of the NICU admission of term neonates on the risk of long-term childhood mortality. METHODS: A single-center case-control retrospective study between 2005 and 2019, including all in-hospital ≥ 37 weeks' gestation singleton live-born neonates. The center perinatal database was linked with the birth and death certificate registries of the Israeli Ministry of Internal Affairs. The primary aim of the study was to study the association between NICU admission and childhood mortality throughout a 15-year follow-up period. RESULTS: During the study period, 206,509 births were registered; 192,527 (93.22%) term neonates were included in the study; 5292 (2.75%) were admitted to NICU. Throughout the follow-up period, the mortality risk for term neonates admitted to the NICU remained elevated; hazard ratio (HR), 19.72 [14.66, 26.53], (p < 0.001). For all term neonates, the mortality rate was 0.16% (n = 311); 47.9% (n = 149) of those had records of a NICU admission. The mortality rate by time points (ratio1:10,0000 births) related to the age at death during the follow-up period was as follows: 29, up to 7 days; 20, 7-28 days; 37, 28 days to 6 months; 21, 6 months to 1 year; 19, 1-2 years; 9, 2-3 years; 10, 3-4 years; and 27, 4 years and more. Following the exclusion of congenital malformations and chromosomal abnormalities, NICU admission remained the most significant risk factor associated with mortality of the study population, HRs, 364.4 [145.3; 913.3] for mortality in the first 7 days of life; 19.6 [12.1; 32.0] for mortality from 28 days through 6 months of life and remained markedly elevated after age 4 years; HR, 7.1 [3.0; 17.0]. The mortality risk related to the NICU admission event, adjusted for admission diagnoses remained significant; HR = 8.21 [5.43; 12.4]. CONCLUSIONS: NICU admission for term neonates is a pondering event for the risk of long-term childhood mortality. This group of term neonates may benefit from focused health care.

NICU Admission for Term Neonates in a Large Single-Center Population: A Comprehensive Assessment of Risk Factors Using a Tandem Analysis Approach.

Objective: Neonatal intensive care unit (NICU) admission among term neonates is associated with significant morbidity and mortality, as well as high healthcare costs. A comprehensive NICU admission risk assessment using an integrated statistical approach for this rare admission event may be used to build a risk calculation algorithm for this group of neonates prior to delivery. Methods: A single-center case−control retrospective study was conducted between August 2005 and December 2019, including in-hospital singleton live born neonates, born at ≥37 weeks' gestation. Analyses included univariate and multivariable models combined with the machine learning gradient-boosting model (GBM). The primary aim of the study was to identify and quantify risk factors and causes of NICU admission of term neonates. Results: During the study period, 206,509 births were registered at the Shaare Zedek Medical Center. After applying the study exclusion criteria, 192,527 term neonates were included in the study; 5292 (2.75%) were admitted to the NICU. The NICU admission risk was significantly higher (ORs [95%CIs]) for offspring of nulliparous women (1.19 [1.07, 1.33]), those with diabetes mellitus or hypertensive complications of pregnancy (2.52 [2.09, 3.03] and 1.28 [1.02, 1.60] respectively), and for those born during the 37th week of gestation (2.99 [2.63, 3.41]; p < 0.001 for all), adjusted for congenital malformations and genetic syndromes. A GBM to predict NICU admission applied to data prior to delivery showed an area under the receiver operating characteristic curve of 0.750 (95%CI 0.743−0.757) and classified 27% as high risk and 73% as low risk. This risk stratification was significantly associated with adverse maternal and neonatal outcomes. Conclusion: The present study identified NICU admission risk factors for term neonates; along with the machine learning ranking of the risk factors, the highly predictive model may serve as a basis for individual risk calculation algorithm prior to delivery. We suggest that in the future, this type of planning of the delivery will serve different health systems, in both high- and low-resource environments, along with the NICU admission or transfer policy.

"Your baby has Down syndrome": what is the preferable way to inform parents?

OBJECTIVE: We tested whether mothers of neonates with Down syndrome (DS) prefer to get the diagnosis after delivery in a one-step approach or in a two-step one (information about suggestive findings, followed by additional explicit meeting). METHODS: Mothers were asked whether (1) they had been informed in one or two steps; (2) they would have preferred the other approach. RESULTS: Of 45 women who completed the questionnaires, 18 (40%) had been informed in a one step and 27 (60%) in two steps. Thirteen of the 18 mothers (72.2%) informed in one step were satisfied with the manner they had been informed, while 19 (70.4%) in the two-step group expressed satisfaction. CONCLUSION: Mothers were generally satisfied with the method chosen with them. We speculate that an adaptive, supportive, empathic, caring and honest approach, taking into consideration family cultural and religious backgrounds may be able to optimize the delivery of such news.

Ethical Dilemmas in Neonatology - Four Theoretical Cases and Three Monotheistic Approaches: A Pilot Study.

BACKGROUND: Israel's population is diverse, with people of different religions, many of whom seek spiritual guidance during ethical dilemmas. It is paramount for healthcare providers to be familiar with different religious approaches. OBJECTIVES: To describe the attitudes of the three major monotheistic religions when encountering four complex neonatal situations. METHODS: A questionnaire related to four simulated cases was presented to each participant: a non-viable extremely premature infant (case 1), a severely asphyxiated term infant with extensive brain damage (case 2), a small preterm infant with severe brain hemorrhage and likely extensive brain damage (case 3), and a term infant with trisomy 21 syndrome and a severe cardiac malformation (case 4). RESULTS: Major differences among the three religious opinions were found in the definition of viability and in the approach towards quality of life. CONCLUSIONS: Neonatologists must be sensitive to culture and religion when dealing with major ethical issues in the neonatal intensive care unit.

Assessment of maternal GBS colonization and early-onset neonatal disease rate for term deliveries: a decade perspective.

Objective To assess the maternal group B streptococcal (GBS) colonization rate and neonatal early-onset GBS (EOGBS) disease in term deliveries, a decade apart. Methods This was a retrospective computerized study between 2005 and 2016. A universal GBS culture-based approach gradually replaced the GBS risk-oriented screening. A vaginal-rectal culture taken at 35-37 weeks was recorded at admission for delivery. Results We identified 149,910 term deliveries during the study period. GBS status was recorded in 53,879 (35.9%) cases. The GBS screening rate constantly increased from 20% in 2005 to 47.5% in 2016. GBS colonization rates significantly decreased, from 50.3% in 2005 to 31.7% in 2016, P<0.001. Overall, EOGBS disease was diagnosed in 37 term neonates (0.25 per 1000 live births.). The rate of EOGBS in neonates decreased dramatically from 0.361 per 1000 deliveries between 2005 and 2009 to 0.19 per 1000 deliveries between 2010 and 2016 (P<0.05). During the latter period, over 35% of the deliveries were screened for GBS. Remarkably, 64.9% of the EOGBS originated in the non-screened population. Conclusion The universal screening policy was associated with a significant decrease in neonatal EOGBS and therefore should be adopted. Further national surveillance studies should be performed in order to validate this approach.

The mortality of very low birth weight infants: the benefit and relative impact of changes in population and therapeutic variables.

OBJECTIVE: Very low birth weight (VLBW, ≤1500 g) infants' mortality rates have decreased markedly. We aimed to quantify the relative contribution of changes in the distribution of population characteristics and changes in specific mortality rates on the decline in mortality rates of VLBW infants. STUDY DESIGN: A population-based observational study of the Israel national VLBW infant database. The study population comprised singleton VLBW infants of 24-32 weeks' gestation born during the epochs 1995-2000 (n = 3728) and 2006-2010 (n = 3246). The Kitagawa methodology was applied to determine the contribution of changes in demographic and perinatal characteristics and changes in specific mortality rates on the decline in mortality between the periods. RESULTS: During the study epochs, VLBW infant mortality rates decreased from 19.7 to 13.8%. Of the 5.9% decrease in mortality, 60.6% was attributed to the decrease in specific mortality rates and 39.4% to changes in the proportions of population characteristics and therapies, predominantly early initiation of prenatal care (8.1%), antenatal steroids (25.1%), and cesarean delivery (8.1%). For most of the demographic and perinatal categories considered the relative contribution of changes in their proportions was <3%, whereas >97% could be attributed to changes in the specific mortality rates for these characteristics. CONCLUSIONS: The decrease in preterm VLBW infant mortality was attributable predominantly to changes in variable specific mortality rates whereas changes in the proportions of demographic, perinatal risk factors, and therapies had a limited impact on VLBW infant mortality. Future assessment of determinants of VLBW infant mortality data should be dissected by discriminatory models.

Opinions of Israeli neonatologists about life and death decisions in neonates.

BACKGROUND: In 2005, the Israeli parliament passed the "law of dying patients" legalizing life and death decisions (do not resuscitate) in patients with life expectancy less than 6 months. OBJECTIVE: To determine whether ethnic and religious backgrounds (both religion and religiosity) influence neonatologists' attitudes in simulated clinical situations and opinions about the new law. DESIGN/METHODS: Prospective design, using standard questionnaire sent to all 155 board-certified practising Israeli Neonatologists. The questionnaire sought demographic and descriptive data, personal opinions regarding four simulated cases, and opinions about five statements regarding variables that may influence decision-making. Statistical analyses were by stepwise backward regression analysis, linear regression, and Kruskal-Wallis tests, wherever indicated. RESULTS: Sixty-nine percent of the neonatologists replied, representing 27 NICUs out of the 29 NICUs in Israel. Most neonatologists would respect the wish of the family as long as it would be within the limits of the law or their personal beliefs. In stepwise regression analysis, religion, religiosity, age, gender, experience, or country of training did not influence significantly the neonatologists' opinions or their decisions in simulated practice. Most neonatologists felt that Ethical Committees had no role in NICUs and were seldom consulted. Most felt that likelihood of severe handicap was critical in decision-making. Issues related to treatment cost of a handicapped or dying infant, as well as impact of a handicapped infant on family's well-being, were not deemed critical. CONCLUSION: Israeli neonatologists appear to be a relatively homogeneous group in end-of-life decisions, regardless of their ethnic, religious, or religiosity background.

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

BACKGROUND: Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. STUDY DESIGN: Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. RESULTS: Twenty-nine neonates with NE and 84 age-matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. CONCLUSION: Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.

"The next-generation": Long-term reproductive outcome of adults born at a very low birth weight.

BACKGROUND: Preterm birth at very low birth weight (VLBW, <1500g) has a multitude of consequences that extend to various aspects of adult life. Little is known about the long-term reproductive outcome of VLBW that survive to adulthood. AIMS: To evaluate the reproductive outcome of VLBW infants who survive to adulthood (next-generation). STUDY DESIGN: Retrospective cohort. SUBJECTS: Infants born at a single tertiary center between the years 1982-1997 who survived to 18years of age (first-generation). OUTCOME MEASURES: The number and the birth weight of offspring from adults born with VLBW were compared to those of other birth weight groups born in the same epoch: 1500-2499g, 2500-3799g (reference group) and ≥3800g. We calculated the ratio of actual compared to expected number of children in the next-generation for extreme birth weight parents, using the reference group as a control group and adjusting for birth year. Thereafter, we measured whether first-generation VLBW had an increased risk for a VLBW in the next-generation. RESULTS: After exclusions, we identified first-generation 67,183 births, including 618 (9.2%) VLBW. There were 193 males and 184 female VLBW infants who survived to adulthood. Both female and male first-generation patients from the VLBW group had half the reproductive rate relative for the normal birth weight group. After adjusting for parental age, male and female VLBW survivors had no significant risk for a VLBW neonate in the next-generation, however, the overall number of are small and may limit any conclusion. CONCLUSION: VLBW children who reach adulthood may be at a significantly lower reproductive capacity.

Fetal Urine Production Rate in Preterm Premature Rupture of Membranes Is Associated with Adverse Neonatal Outcome: A Pilot Study.

AIM: In this study, we evaluate the associations between fetal urinary production rate (FUPR), measured by ultrasound, and adverse neonatal outcome in women with preterm premature rupture of membranes (PPROM). METHODS: We conducted a prospective pilot cohort of singleton pregnancies complicated by PPROM occurring at gestational week 24 or later managed until spontaneous labor (after 48 h of admission), chorioamnionitis, or induction by protocol at 35 + 0 weeks. FUPR was evaluated by 2D sonography at admission (corrected for gestational age). The main neonatal outcome measures were chorioamnionitis, placental inflammatory grading, first neonatal creatinine value, first neonatal dextrose value, length of neonatal intensive care unit (NICU) stay, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH) (grades I-IV), blood transfusions, reduced neonatal urine production rate (<4 mL/kg/h), and early neonatal sepsis. Samples of maternal (at admission) and umbilical cord blood were analyzed for interleukin-6 (IL-6) level. RESULTS: The study included 38 women. Low FUPR was associated with clinical chorioamnionitis, longer NICU hospitalization (p = 0.01), higher rates of NEC or IVH (p = 0.008), and blood transfusion (p = 0.004). CONCLUSIONS: A finding of FUPR on in utero ultrasound examination in pregnancies complicated by PPROM may be indicative of adverse neonatal outcome.

Neonatal characteristics and perinatal complications in neonates with Down syndrome.

The annual rate of Down syndrome (DS) births in Jerusalem is stable, regardless of prenatal screening, and diagnostic measures. We aimed to evaluate our historical cohort for obstetrical characteristics and the neonatal course and complications. We reviewed computerized medical files of neonates with the diagnosis of DS born in the four main hospitals in Jerusalem between the years 2000 and 2010 and evaluated for maternal history and primary neonatal hospitalization. A total of 403 neonates were diagnosed with DS. The average maternal age was 35.6 years, 73% were born via spontaneous vaginal delivery. In all gestational ages, the mean birth weight and head circumference percentiles were significantly lower than the general population (P < 0.001 for both) and at each week the HC percentile was lower than the weight percentile (P < 0.0001), worse among males. Mortality during the primary hospitalization was 3.7%. The most common anomalies were cardiac (79%) with either congenital defects or functional abnormalities, neither influenced the length of hospitalization. The main reasons for prolonged hospitalization were prematurity and anomalies of other (non-cardiac) organs. Common perinatal complications included respiratory failure or need for oxygen supplementation (32%), hyperbilirubinemia (23%), sepsis (6.4%), and feeding difficulties (13%). About 84% were fed by human milk; of those, two thirds were exclusively breast-fed and one third were supplemented with infant formula. In conclusion, infants with DS were small for gestational age with relatively reduced head circumference. Despite the increased rate of congenital anomalies and perinatal complications, most infants were discharged home in good medical condition and were exclusively breastfed.

Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome.

OBJECTIVE: To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. STUDY DESIGN: Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. RESULTS: tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. CONCLUSIONS: T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH.

Care for infants born at 23 weeks gestational age: 5 years' experience from a large medical center.

OBJECTIVES: Assessing parental choice regarding care of infants born at 23 weeks' gestation. METHODS: Neonatal records review. RESULTS: During 2010-2014, of 26 births (33 infants), 13 families (17 newborns) conceded comfort care only with no survivors, while 13 families (16 babies) requested full medical care and three survived. With birth year, gender, multi-fetal pregnancy, assisted reproductive technology, religious background and specialization of physician counseling at delivery as independent variables, none significantly affected parental decision; yet, that decision impacted outcome. CONCLUSIONS: Parental choice regarding infants born at 23 weeks' gestation cannot be predicted from demographics; counseling should concentrate on local experience/outcome.

Delivery of a very low birth weight infant and increased maternal risk of cancer and death: a population study with 16 years of follow-up.

BACKGROUND: Pregnancy complications represent sentinel events for women's future health. We investigated whether delivery of a very low birth weight (VLBW) infant is associated with increased maternal risk for future incidence of maternal cancer and death. METHODS: This is a population-based cohort study of linked Israeli Ministry of Health datasets between 1995 and 2011. Women delivering a live singleton <1,500 g infant (VLBW group) were compared with women delivering a live singleton, 3,000-3,500 g (control). The first pregnancy eligible for entry into the study, the "index pregnancy," reflected exposure status for each participant. Primary outcomes were maternal cancer and death. Cancer diagnoses were further classified by primary site. Cox regression models adjusted for follow-up period and maternal characteristics at index pregnancy: Age at delivery, ethnicity, years of education, marital status, and previous cancer afforded calculation of hazard ratios (HR) and 95% confidence intervals (CI). FINDINGS: During the study period, 982,091 mothers with 2,243,736 live births were identified; of these, 13,773 births were VLBW eligible for inclusion in the study and 448,743 births were controls. Groups differed significantly by average follow-up and all maternal characteristics evaluated. Overall rate of cancers and death was significantly increased for VLBW women compared to controls: 18.4 versus 15.7% and 7.3 versus 3.2%, both p < 0.0001. The Cox model adjusted for maternal characteristics showed significantly increased risk of cancer (all sites) in the VLBW women: HR 1.18 (95% CI 1.02-1.37) and for death: HR 2.13 (95% CI 1.68-2.71), and an increased combined risk of both outcomes: HR 1.4 (95% CI 1.23-1.59). INTERPRETATION: The delivery of a VLBW newborn is an independent lifetime risk factor for subsequent maternal cancers and death. These women may benefit from targeted cancer screening and counseling.

The effects of maternal age and parity on maternal and neonatal outcome.

PURPOSE: Delayed childbearing is increasingly common; hence, concerns emerge regarding potential for additional risks of delivery at advanced maternal age (AMA; ≥35 years). In this study, we sought to assess impact of AMA and parity on maternal and perinatal outcomes. METHODS: In this retrospective single-center study (July 2005 to October 2011), we compared spontaneously-conceived singleton births of AMA mothers with spontaneously-conceived singletons of mothers aged 24-27 years. Maternal outcomes: incidence of diabetes, hypertension, and emergency cesarean sections (ECS). Neonatal outcomes: prematurity, birth weight, incidence of small or large for gestational age infants (SGA/LGA, respectively), low birth weight (LBW), and 5'-Apgar scores. Sub-groupings of maternal age were 35-38, 39-42, or 43-47 years; prematurity as <34 or <37 weeks; AMA parity as primiparous, 2-5 births, 6-9 births, or ≥10 births. Binary logistic regression was used for multivariate analyses. RESULTS: Of 24,579 eligible women, 11,243 were AMA (14.0% total singleton births) and 13,336 were aged 24-27 years (16.7% total singleton births) at delivery. There were no maternal or perinatal deaths. Incidence of maternal hypertension and diabetes was significantly greater in AMA, especially oldest AMA. AMA including primiparous had significantly more ECS than younger including primiparous controls, respectively, and were more likely to deliver LGA neonates. Primiparous AMA women did not have increased incidence of LGA babies but significantly increased incidence of SGA infants. CONCLUSION: AMA, especially primiparous, has more adverse maternal and neonatal outcomes than younger women; however, these did not include mortality. Consistent antenatal care may explain this.

Population-based trends in mortality and neonatal morbidities among singleton, very preterm, very low birth weight infants over 16 years.

BACKGROUND: Improved survival of singleton very preterm, very low birth weight (VPTVLBW) infants has been associated with increasing rates of severe neonatal morbidities. AIM: To assess changes in mortality and neonatal morbidities among singleton VPT-VLBW infants. STUDY DESIGN: Population-based observational study of data collected by the Israel Neonatal Network. SUBJECTS: 10,705 singleton VPT-VLBW infants born at 24-32 gestational weeks in 1995-2010. OUTCOME MEASURES: Mortality and major neonatal morbidities over 3 time periods: 1995-2000, 2001-2005, and 2006-2010. Major neurological morbidities comprised intraventricular hemorrhage grades 3-4, periventricular leukomalacia and retinopathy of prematurity grades 3-4. RESULTS: The mortality rate decreased over time from 20.2% to 13.8% for all birth weight and gestational age groups. Compared to the 1995-2000 period, the adjusted odds ratios (aORs) (95% confidence intervals,) for mortality in 2001-2005 and 2006-2010 were 0.78 (0.67-0.90) and 0.72 (0.62-0.84), respectively. The combined outcomes of death or major neurological morbidities, aOR 0.74 (0.65-0.84) and death or major neurological morbidities and/or bronchopulmonary dysplasia aOR 0.85 (0.75-0.96) decreased significantly between the first and last periods. A significant improvement in mortality rates and survival without one or more major neonatal morbidity was observed for all birth weight and gestational age groups. Among 8,886 surviving infants the rates of major neurological morbidities decreased from 16.4% to 12.8%, aOR 0.80 (0.68-0.95). CONCLUSION: The improving survival of singleton VTP-VLBW infants was not associated with a concomitant increase in the risk for major neonatal neurological morbidities among surviving infants. Bronchopulmonary dysplasia, however, remained a significant burden. This analysis emphasizes the need to direct efforts towards the prevention and treatment of adverse respiratory sequelae.

Neonatal outcome after preimplantation genetic diagnosis.

OBJECTIVE: To examine whether embryo biopsy for preimplantation genetic diagnosis (PGD) influences neonatal outcomes. DESIGN: Prospective follow-up cohort. SETTING: Tertiary university-affiliated medical center. PATIENT(S): 242 children born after PGD, 242 children born after intracytoplasmic sperm injection (ICSI) (158 singletons and 42 twins pairs in each group), and 733 children born after a spontaneous conception (SC) (493 singletons, 120 twins pairs), matched for maternal age, parity, and body mass index. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Gestational age, birth weight, prematurity (<37 and <34 weeks), low birth weight (<2,500 g, very low birth weight, <1,500 g), and intrauterine growth restriction (<10th percentile for gestational age). RESULT(S): For singletons, the mean birth weight was higher after SC compared with ICSI but not compared with PGD. Mean gestational ages were lower after PGD and ICSI compared with SC. The low birth weight and intrauterine growth restriction rates were 4.4%, 12.0%, and 5.7% and 5.1%, 9.5%, and 5.5% for PGD, ICSI, and SC, respectively. Similar results were found when controlled for the number of embryos transferred and cryopreservation. The results for twins exhibited similar but less statistically significant trends. Polar body and blastomere biopsies provided similar outcomes. CONCLUSION(S): Embryo biopsy itself did not cause intrauterine growth restriction or low birth weight compared with SC, despite lower gestational ages with PGD. The worsened outcomes in ICSI compared with PGD pregnancies may be due to the infertility itself.

Vitamin D receptor polymorphism FokI is associated with spontaneous idiopathic preterm birth in an Israeli population.

OBJECTIVE: The active form of vitamin D (1,25[OH]2D3) has been established to have potent anti-proliferative, immuno-modulatory, and anti-microbial action in addition to its effects on bone. The nuclear vitamin D receptor (VDR) is expressed in the placenta-decidua, regulating genes associated with implantation and implantation immuno-tolerance. If VDR polymorphisms regulate VDR functionality at the placenta-decidua interface, VDR genotypes may be involved in idiopathic preterm birth (PTB). STUDY DESIGN: Maternal and fetal (umbilical cord) blood samples from 33 Jewish and Arab mothers with PTB of a singleton neonate were compared to 98 samples from Jewish and Arab maternal and fetal blood samples from full-term, uncomplicated singleton births. Maternal age and ethnicity were comparable between groups. PCR amplification/digestion identified the VDR SNPs: FokI, ApaI, TaqI, and BsmI. RESULTS: Allele frequency for the FokI VDR in maternal blood samples from preterm births (but not umbilical cord samples) was significantly different (p=0.01) from that in maternal and umbilical cord blood samples from full-term singleton births, with an odds ratio for FokI carriers of 3.317 (95% CI, 1.143, 9.627) for preterm birth. The FokI VDR variant may therefore be a maternal risk trait for PTB among these women. CONCLUSION: This study may support a future platform for the study of vitamin D during pregnancy and treatment of selective target populations with vitamin D and/or VDR "tissue-specific therapeutic intervention" for prevention of PTB.

The prenatal diagnosis of isolated fetal varix of the intra-abdominal umbilical vein is associated with favorable neonatal outcome at term: a case series.

OBJECTIVE: Varix of the fetal intra-abdominal umbilical vein (VFIUV) has been reported to be associated with an increased risk of adverse perinatal outcome and especially with intra-uterine fetal demise (IUFD). Induction of preterm birth, as early as 32-34 weeks gestation has been suggested to minimize this risk. We aimed to evaluate our center experience with the antenatal diagnosis of VFIUV and review the relevant literature. METHODS: This is a retrospective case series of all cases (between 2004 and 2009) where the sonographic antenatal diagnosis of VFIUV was registered at any gestational age (GA). Ultrasound, maternal and newborn electronic medical records were used. Descriptive statistics were employed as appropriated and correlation coefficient (r) calculated. RESULTS: We identified 24 women with fetuses, with isolated VFIUV (excluding one lost-to-follow-up). GA at diagnosis was 30.5 ± 4.4 weeks; 13 (56.5 %) cases were diagnosed <32 weeks. The mean VFIUV diameter was 13 ± 2.9 (range 9-20) mm and turbulent flow was reported in 7 cases (30.4 %). GA at birth was 37 ± 2.5 weeks. The small for gestational age rate was 4 % (1/23), while no case of IUFD occurred. The group induction of labor rate was 65.2 %, while 43 % (10/23) due to the diagnosis of VFIUV alone: 17 % (4/23) preterm and 26 % (6/23) at term. The cesarean rate was 17 % (4/23) and NICU admission was required for five neonates (21.7 %). The preterm induction of birth was related to a significantly increased risk for cesarean and neonatal morbidity (p = 0.015; p = 0.029, respectively). The mode of delivery was not associated with the GA at diagnosis, size/type of flow of VFIUV (r = 0.101; r = 0.727; r = 0.671, respectively) overall (r) = 0.4. All fetuses were live-born with normal follow-up at 2-60 months. CONCLUSION: Isolated VFIUV has a favorable perinatal outcome at term, unrelated to the structural and flow characteristics of VFIUV. We show that follow-up for growth abnormalities with no preterm induction of birth is a safe maternal and neonatal approach.

Correlation of bacterial type and antibiotic sensitivity with maternal antibiotic exposure in early-onset neonatal sepsis.

BACKGROUND: Antibiotic administration during pregnancy as group B Streptococcus prophylaxis or as treatment of maternal conditions has become widespread. OBJECTIVE: To assess whether bacterial type and antibiotic resistance in early-onset neonatal sepsis are associated with maternal antibiotic use. METHODS: All positive blood and/or cerebrospinal fluid cultures (case-only study) and respective antibiotic sensitivities from newborns delivered in Shaare Zedek Medical Center, Jerusalem, Israel, between 01/01/1997 and 31/01/2007, taken during the first 72 h of life, were studied. Clinical and demographic data were obtained from the medical records of the infant/mother dyads. Three groups were defined by type of maternal antibiotic exposure: (1) no exposure, (2) intrapartum antibiotic prophylaxis (IAP), (3) antepartum antibiotic exposure during the month prior to delivery and extending into delivery or with subsequent IAP (AAE). Factors potentially associated with Gram-negative bacteremia and resistance to ampicillin were analyzed using multivariate logistic regression. RESULTS: Ninety-seven different organisms grew from 94 infants (1.03 per 1,000 live births). By univariate analysis, AAE, gestational age ≤ 32 weeks, chorioamnionitis and rupture of membranes ≥ 18 h, were significantly associated with both Gram-negative sepsis and antibiotic resistance. By multivariate analysis, AAE was significantly associated with both outcomes, while gestational age ≤32 weeks was only associated with antibiotic resistance. CONCLUSIONS: AAE for more than 24 h is associated with an increased proportion of Gram-negative organisms and ampicillin resistance in early-onset neonatal sepsis. Antepartum antibiotic therapy and its ramifications need to be continuously monitored and prospectively studied.