Breastfeeding following bariatric surgery among obese women with and without diabetes mellitus.

BACKGROUND: Information on exclusive breastfeeding (BF) and BF initiation following bariatric surgery (BS) among obese women with diabetes mellitus (DM) and without DM (non-DM) is limited. METHODS: Retrospective cohort study. Obesity was defined by BMI (kg/m2) as grade 1 (30-34.9), grade 2 (35-39.9) or grade 3 (≥40). The 65 women in the DM group (40 women with gestational, 19 with Type 2 and 6 with Type 1) was similar to 84 with non-DM in BS type: Roux-en-Y (51 vs 55%), sleeve gastrectomy (32 vs 35%), laparoscopic gastric banding (17 vs 7%) and gastro-duodenal anastomosis (0 vs 4%). RESULTS: Women with DM were older (35 vs 33y), of advanced age (54 vs 27%), with higher prevalence of grade 3 obesity (66 vs 46%), chronic hypertension (31 vs 10%), delivery of late-preterm infants (23 vs 10%) and neonatal hypoglycemia (25 vs 12%). Although infant feeding intention was similar: BF (66 vs 79%), partial BF (9 vs 7%) or formula (25 vs 14%), at discharge women with DM had lower exclusive BF (29 vs 41%) and BF initiation rates (68 vs 76%) than those with non-DM. Women with grade 3 obesity (52% were DM) differed from those with grades 1-2 (34% were DM) in exclusive BF (27 vs 52%), and BF initiation rates (66 vs 86%). CONCLUSION: After BS, women with DM, especially those with grade 3 obesity, had higher rates of chronic hypertension and preeclampsia and lower rates of exclusive BF and BF initiation than those who had DM but had less severe obesity.

Breastfeeding initiation among women with chronic hypertension superimposed on pregestational diabetes mellitus.

OBJECTIVE: To compare breastfeeding (BF) initiation among 317 women with chronic hypertension (CHTN) and 106 women with CHTN superimposed on pregestational diabetes (CHTN-DM) who intended exclusive or partial BF. METHODS: Retrospective cohort study of women who delivered at≥34 weeks of gestation. At discharge, exclusive BF was defined by direct BF or BF complemented with expressed breast milk (EBM) while partial BF was defined by formula supplementation. RESULTS: CHTN and CHTN-DM groups were similar in prior BF experience (42 vs 52%), intention to BF exclusively (89 vs 79%) and intention to partially BF (11 vs 21%). Women in the CHTN group were younger (31 vs 33y), more likely primiparous (44 vs 27%), and delivered vaginally (59 vs 36%) at term (85 vs 75%). Women in the CHTN-DM group had higher repeat cesarean rates (32 vs 18%), preterm birth (25 vs 15%), neonatal hypoglycemia (42 vs 14%) and NICU admission (38 vs 16%). At discharge, exclusive BF rates among CHTN was higher (48 vs 19%), while rates of partial BF (34 vs 44%) and FF (18 vs 37%) were lower than in the CHTN-DM group. BF initiation (exclusive plus partial BF) occurred in 82%of CHTN and in 63% of CHTN-DM. CONCLUSION: Although intention to BF was similar, BF initiation rates were higher for the CHTN compared to the CHTN-DM group. Exclusive BF was low in the CHTN and even lower in the CHTN-DM group signaling the need for targeted interventions if BF initiation rates are to be improved.

Breastfeeding initiation among women with preeclampsia with and without severe features.

BACKGROUND: Timely delivery and magnesium sulfate (MgSO4) are mainstay in the treatment of preeclampsia with severe features (PWSF). Premature delivery, severity of illness and mother-infant separation may increase the risk for breastfeeding (BF) initiation failure. OBJECTIVE: To compare BF initiation among women with late-onset PWSF treated with MgSO4 to women with late-onset preeclampsia without severe features (WOSF) who did not receive MgSO4. METHODS: Retrospective study of 158 women with PWSF and 104 with WOSF who delivered at ≥34 weeks. Intention to BF, formula feed (FF) or partially BF was declared prenatally. At discharge, exclusive BF included direct BF or direct BF with expressed breast milk (EBM). RESULTS: PWSF and WOSF groups were similar in age, race, and obstetric history. PWSF and WSOF differed in primiparity (65 & 51%), late preterm births (73 vs 15%), admission to NICU (44 &17%) and mother (5 & 4d) and infant (6 & 3d) hospital stay. Both groups were similar in intention to BF (80 & 84%), to FF (16 & 13%) and to partially BF (5 & 5%). At discharge, exclusive BF (37 & 39%), partial BF (33 & 31%) and FF (30 & 30%) were similar. Exclusive BF in the PWSF group was 43% direct BF, 28% direct BF and EBM and 29% EBM alone whereas in the WOSF group exclusive BF was 93% direct BF and 7% direct BF and EBM. CONCLUSION: BF initiation rates for women with PWSF and WOSF were similar. EBM alone or with direct BF enabled infants in the PWSF group to exclusively BF at discharge.

Prior breastfeeding experience and infant feeding at discharge among women with pregestational diabetes mellitus.

OBJECTIVE: To compare multiparous women with pregestational diabetes mellitus (PGDM) with and without prior breastfeeding (BF) experience and to ascertain their infants' feeding type during hospitalization and at discharge. METHODS: A retrospective cohort study of 304 women with PGDM who delivered at ≥34 weeks gestational age (GA). Prior BF experience and infant feeding preference was declared prenatally. At discharge, BF was defined as exclusive or partial. RESULTS: BF experience and no experience groups were similar in diabetes type 1 and 2, race and number of pregnancies. Women with no experience had more spontaneous abortions (35 vs 27%), fewer term deliveries (51 vs 61%) and living children (median 1 vs 2). In the current pregnancy, mode of delivery: vaginal (36 & 37%), cesarean (64 & 63%), birthweight (3592 & 3515 g), GA (38 & 37 w), NICU admission (14 & 11%) and hypoglycemia (44 & 43%) were similar. Women with experience intended to BF (79 vs 46%), their infants' first feeding was BF (64 vs 36%) and had lactation consults (96 vs 63%) more often than those without experience. At discharge, women with BF experience were different in rate of exclusive BF (33 vs 11%), partial BF (48 vs 25%) and formula feeding (19 vs 64%). CONCLUSION: Prior BF experience leads to better BF initiation rates while the absence of BF experience adds a risk for BF initiation failure. A detailed BF history could provide insight into obstacles that lead to unsuccessful BF experiences and may help define appropriate preventive or corrective strategies.

In-hospital formula supplementation and breastfeeding initiation in infants born to women with pregestational diabetes mellitus.

OBJECTIVE: To ascertain the rate of in-hospital supplementation as it relates to early breastfeeding (BF) and early formula feeding (FF) and its effects on BF (exclusive and partial) at the time of discharge for infants born to women with pregestational diabetes mellitus (PGDM). METHODS: Retrospective cohort investigation of 282 women with PGDM who intended to BF and their asymptomatic infants admitted to the newborn nursery for blood glucose monitoring and routine care. Early feeding was defined by the initial feeding if given within four hours of birth. RESULTS: Of the 282 mother-infant dyads, for 134 (48%) early feeding was BF and for 148 (52%) early feeding was FF. Times from birth to BF and FF (median 1 hr, 0.3-6) were similar, while the time to first BF for those who FF and supplemented was longer (median 6 hr., 1-24). Ninety-seven infants (72%) who first BF also supplemented. Of these, 22 (23%) BF exclusively, 67 (69%) BF partially and 8 (8%) FF at discharge. One hundred seventeen (79%) who first FF also supplemented. Of these, 21 (18%) BF exclusively, 76 (65%) BF partially and 20 (17%) FF at discharge. CONCLUSION: Regardless of the type of first feeding, the majority of infants born to women with PGDM require supplementation. Even when medically indicated, in-hospital supplementation is an obstacle, albeit not absolute, to exclusive BF at discharge. Parents should be reminded that occasional supplementation should not deter resumption and continuation of BF.

Early feeding, hypoglycemia and breastfeeding initiation in infants born to women with pregestational diabetes mellitus.

OBJECTIVE: To examine the effects of early breastfeeding (eBF) or early formula feeding (eFF) on hypoglycemia and on BF initiation in infants born to women with pregestational diabetes mellitus (PGDM) who intended to BF. METHODS: Retrospective cohort investigation of 554 women with PGDM and their infants (IDMs) who delivered during 2008-2016. The first feeding (BF or FF) was considered early if given within 4 hours from birth. RESULTS: 282 (51%) IDMs were admitted to the Well Baby Nursery. Of the 134 IDMs whose early feeding was BF, hypoglycemia affected 30% which was corrected with oral feedings in 78% of the cases. At discharge, 49% BF exclusively while 45% BF partially. Of the 148 IDMs whose early feeding was FF, hypoglycemia affected 40% which was corrected with oral feedings in 69% of the cases. At discharge, 14% BF exclusively while 48% BF partially. There were 272 (49%) IDMs admitted to the NICU. Their early feeding was BF (14%) and FF (86%). Hypoglycemia developed in 50% and 43% of these groups, respectively. Benefits of early feedings on hypoglycemia were masked by the routine use of IV dextrose infusions. At discharge, early BF led to exclusive BF in 45% and partial BF in 50% of the cases. Early FF led to exclusive BF in 17% and partial BF in 42% of the cases. CONCLUSIONS: Early and continued feeding (BF preferably or FF if BF is not feasible) should be the first line of treatment for hypoglycemia. Early BF is paramount for BF initiation. Early FF is an obstacle, albeit not absolute, to BF initiation, thus it should not deter continued efforts to start or resume BF.

Decreasing NICU admissions of asymptomatic infants of women with pregestational diabetes mellitus improves breastfeeding initiation rates.

BACKGROUND: Asymptomatic infants born to women with pregestational diabetes mellitus (PGDM) are usually admitted to the well baby nursery (WBN) while those who are symptomatic or in need of specialized care are admitted to the neonatal intensive care unit (NICU). OBJECTIVE: To determine if changes in the NICU admission rate of asymptomatic infants born to women with PGDM during two different epochs affected breastfeeding (BF) initiation rates. DESIGN/METHODS: Retrospective cohort investigation of 386 women with PGDM and their infants who delivered in 2008-11 (epoch 1) and 457 who delivered in 2013-16 (epoch 2) at a single institution. RESULTS: NICU admissions: Comparison between epoch 1 and epoch 2 showed a decrease in the number of admissions from 243 (63%) to 175 (38%) *(chi square *p < 0.05). Respiratory distress (39 and 43%) and prematurity (28 and 23%) as admission diagnoses remained unchanged. Admissions for prevention of hypoglycemia declined (32% to 21%)*. At discharge from the NICU, exclusive BF (12 to 19%)* and any BF increased (41 to 55%)* while formula feeding (FF) decreased (59 to 45%)*. Admission to the NICU remained a strong predictor of BF initiation failure (a OR 0.6, 95% , CI 0.4-0.9, p 0.005).WBN admissions: Comparison between epoch 1 and epoch 2 showed an increase in the number of admissions from 143 (37%) to 282 (62%)*. The incidence of hypoglycemia (31% and 38%) and its correction with oral feedings (76% and 71%) remained unchanged. At discharge from the WBN, exclusive BF (15 to 27%)* and any BF (52 to 62%)* increased while FF decreased (48 to 38%)*. CONCLUSIONS: A decrease in the number of NICU admissions of asymptomatic infants born to women with PGDM is associated with improvements in BF initiation rates.

Failure to initiate breastfeeding among high risk obstetrical patients who intended to breastfeed.

BACKGROUND: In the US, at the time of discharge from the hospital, 79% of women had initiated breastfeeding. Intention to breastfeed is a strong predictor of breastfeeding initiation; however, we reported initiation failure in 45% of women with pregestational diabetes who intended to breastfeed. Information regarding intention and initiation among women with other high risk obstetrical conditions (HROB) remains scarce. OBJECTIVE: To ascertain demographic and clinical factors associated with breastfeeding initiation failure among women with HROB conditions who intended to breastfeed. METHODS: The study population is comprised of 89 women with diabetes (DM), 57 who were receiving treatment for substance abuse (SA), 51 women diagnosed with miscellaneous (MISC) conditions and 32 with history of preterm labor/delivery (PTL/D). Intention to exclusively breastfeed or in combination with formula (breastfed/FF) was ascertained prenatally. Breastfeeding was considered initiated if at discharge ≥50% of their infant feedings were maternal milk. Statistics include chi-square, Wilcoxon's and logistic regression (p < 0.05). RESULTS: Of all women, 59% initiated any breastfeeding. Intention to breastfeed/FF, lack of mother-infant contact during the first hour following birth and limited lactation consultation were predictive of initiation failure. The odds of initiation failure were 2.3 times higher among women who wished to breastfeed/FF as compared to those who wished to exclusively breastfeed. Women from the SA group had lower rates of initiation failure than the other three HROB groups. CONCLUSION: Intention to breastfeed among women with diverse HROB conditions is similar to that of the general population; however, initiation rates are disappointingly low. Intention to exclusively breastfeed results in fewer initiation failures. Prenatal intention to combine breast and formula feeding characterize women who may benefit from specific educational programs.

Neonatal outcomes of macrosomic infants of diabetic and non-diabetic mothers.

OBJECTIVE: To compare neonatal outcomes (including breastfeeding (BF) initiation) of 170 macrosomic IDM with that of 739 macrosomic nIDM. DESIGN/METHODS: Retrospective cohort investigation of all macrosomic infants born consecutively over a four-year period (2008-2011). Macrosomic (birth weight ≥4000 g) IDM included 100 infants whose mothers had gestational diabetes and 70 whose mothers had pregestational diabetes. RESULTS: IDM were more likely to be delivered by cesarean to obese women while nIDM were more likely to be delivered vaginally to younger women with a higher level of education. Ethnic distribution (60% white, 20% black, 10% Hispanic and 10% Asian or African) was similar in each group. Forty-nine percent of IDM and 7% of nIDM required NICU admission. Respiratory disorders (mainly TTNB) affected 21% of IDM and 3% of nIDM while hypoglycemia was observed in 36% of IDM and 15% of nIDM. Of the 35 IDM delivered vaginally, 10 were complicated by shoulder dystocia without injury. Conversely, 70 of the 458 nIDM delivered vaginally experienced shoulder dystocia that resulted in 6 limb fractures and 3 brachial plexus injuries. On arrival to labor and delivery, 75% of all women intended to BF; however, at the time of discharge, 65% of women with diabetes and 92% of those without diabetes who intended to BF had initiated BF. CONCLUSIONS: Both macrosomic IDM and macrosomic nIDM are at risk for significant morbidities. Macrosomic IDM carry a higher risk for NICU admissions, leading to maternal-infant separation, and lower BF initiation rates.

Breastfeeding initiation in women with gestational diabetes mellitus.

BACKGROUND: In the United States, breastfeeding initiation (BFI) is reported for 75% of all live births; however, little information is available regarding mothers affected by gestational diabetes mellitus (GDM). OBJECTIVE: To examine feeding practices and factors associated with BFI in women with GDM and their infants. METHODS: A total of 303 GDM (58 late preterm and 245 term) pregnancies were studied. Infant feeding preference was ascertained on admission to labor and delivery. Variables known to influence BFI including maternal age, smoking, obesity, racial and educational characteristics were assessed. RESULTS: On admission 188 women intended to BF, 60 intended to feed formula and 55 were undecided. None of the women who wished to feed formula and 27% of the originally undecided later initiated BF. Regardless of feeding preference 163 (54%) of all mothers initiated BF. Similar BFI rates were found for 176 Class A1 and 127 class A2 women. Logistic regression analysis showed that intention to BF was the most significant predictor of BFI. Factors associated with BFI failure included African American race, lower education, smoking, obesity and admission to NICU. Following delivery 264 (87%) infants received well baby care while 39 (13%) were admitted to the NICU. Among 188 women who intended to BF, BFI involved 81% of 160 infants receiving well baby care and 61% of the 28 admitted to the NICU. CONCLUSIONS: More than half of women with GDM, who intended to BF, initiated BF. BFI failure remains associated with race, lower education level, smoking, obesity, preference for formula feeding and admission to NICU.

Umbilical cord blood as a replacement source for admission complete blood count in premature infants.

OBJECTIVE: We hypothesize that a complete blood count (CBC) with manual differential from umbilical cord blood is equivalent to a CBC with manual differential obtained from the neonate on admission. STUDY DESIGN: A CBC and manual differential was performed on 174 paired umbilical cord blood and admission blood samples from infants <35 weeks gestation. Paired t-test and Pearson's correlation coefficient were the primary statistical tools used for data analysis. RESULT: Cord and admission blood white blood cell (WBC) count, hemoglobin and platelet count all significantly (P<0.0001) correlated with paired neonatal samples (R=0.82, 0.72, 0.76). Admission blood WBC count fell within the variation of WBC count values from currently accepted neonatal admission blood sources. Cord blood hemoglobin was not clinically different than admission hemoglobin (1.0 g dl(-1)). Cord blood platelet counts were not different from admission blood platelet counts (5800 cells per µl, P=0.23). The immature to total granulocyte ratio was not different between samples (P=0.34). CONCLUSION: Umbilical cord blood can be used for admission CBC and differential in premature infants.

Neonatal abstinence syndrome: transitioning methadone-treated infants from an inpatient to an outpatient setting.

OBJECTIVE: Each year in the US ∼50 000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS). The objective of this study is to compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program. STUDY DESIGN: Retrospective review (2007 to 2009). Infants were born to mothers maintained on methadone in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 patients) was inpatient, whereas the combined group (46 patients) was outpatient. RESULT: Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, gestational age (GA) and the incidence of prematurity (34 and 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25 days; P<0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21 days, P<0.01), the cumulative methadone dose was similar (3.6 vs 3.1 mg kg(-1), P=0.42). Follow-up information (at least 3 months) was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤72 h from hospital discharge. Breastfeeding was more common among infants in the combined group (24 vs 8% P<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (34 to 36 weeks GA) was the only predictor for hospital readmission for NAS in both groups (P=0.02, OR 5). Average hospital cost for each infant in the combined group was $13 817 less than in the traditional group. CONCLUSION: A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long-term benefits of the combined approach on infants and their families.

Implementation of a multidisciplinary guideline-driven approach to the care of the extremely premature infant improved hospital outcomes.

AIM: To test the hypothesis that implementing guidelines for the standardized care of the extremely premature infant (<27 weeks) in the first week of life would improve patient outcomes in an all referral NICU. METHODS: Data were collected on all infants <27 weeks gestational age and <7 days of age on admission cared for using these small baby guidelines (SBG), as well as on all age-matched infants admitted the year prior (comparison). RESULTS: Thirty-seven patients were cared for utilizing the SBG and 40 patients were in the comparison group. There were no differences between the groups in gestational age, birthweight or age on admission. There was no difference in survival to discharge (73% SBG, 70% comparison). The mean length of stay for survivors was 112 +/- 38 days SBG and 145 +/- 76 days (p < 0.05) comparison group. Survival without BPD was greater in the SBG group (24%) than in the comparison group (9%; p < 0.05), and survival without severe IVH was greater in the SBG group (65%) than in the comparison group (38%; p < 0.01). CONCLUSIONS: These data demonstrate that applying a unified approach to the care of the extremely premature infant in the first week of life resulted in a decrease in the length of hospitalization and improved patient outcomes.

Postnatal follow-up of antenatal hydronephrosis: a health-care challenge.

OBJECTIVE: To examine our experience with ANH and to determine the success of our postnatal follow-up program. STUDY DESIGN: Charts of mothers and infants seen (2004 to 2008) at our Regional Perinatal Center were reviewed retrospectively. ANH was defined during the third trimester by anterior pelvic diameters as follows: mild 7 to 9, moderate 10 to 14 or severe >or=15 mm. Fetuses with multicystic dysplastic kidney (MCDK) were included. RESULT: Screening of approximately 15 000 ultrasound (US) reports identified 268 fetuses with ANH. After prenatal US surveillance, 88 (33%) fetuses had resolved, while 180 (67%) required postnatal follow-up. These 180 fetuses were diagnosed with mild 38 (21%), moderate 83 (46%) and severe 19 (11%) ANH, uni or bilateral hydroureters 12 (7%), MCDK 19 (10%) and miscellaneous 9 (5%). Postnatal follow-up was successfully established for 75% of infants with hydroureters, 68% for those with MCDK and for 37% of infants with mild, 53% with moderate and 58% with severe ANH. Factors commonly known to influence compliance were not found more frequently among the 91 infants who were lost to follow-up. The only positive predictor for postnatal follow-up was a prenatal consultation with the pediatric urologist. CONCLUSION: Our antepartum program for diagnosis of ANH is accessible and efficient; however, there was an unacceptably high number of infants lost to follow-up. The absence of traditional barriers for compliance highlights the need to explore new ways of improving postnatal follow-up of infants with ANH.

Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?

BACKGROUND: Indomethacin prophylaxis or expectant treatment are common strategies for the prevention or management of symptomatic patent ductus arteriosus (sPDA). OBJECTIVE: To compare the clinical responses of extremely low birth weight (ELBW) infants to indomethacin prophylaxis with that of other infants who were managed expectantly by being treated with indomethacin or surgically only after an sPDA was detected. METHODS: Retrospective cohort investigation of 167 ELBW infants who received indomethacin prophylaxis (study) and 167 ELBW infants (control) treated expectantly who were matched by year of birth (1999 to 2006), birth weight, gestational age (GA) and gender. RESULTS: Mothers of the two groups of infants were comparable demographically and on the history of preterm labor, pre-eclampsia, antepartum steroids and cesarean delivery. Study and control infants were similar in birth weight, GA, low 5 min Apgar scores, surfactant administration, the need for arterial blood pressure control, bronchopulmonary dysplasia and neonatal mortality. Necrotizing enterocolitis, spontaneous intestinal perforations, intraventricular hemorrhage grade III to IV, periventricular leukomalacia and stage 3 to 5 retinopathy of prematurity occurred also with similar frequency in both groups of infants. In the indomethacin prophylaxis group, 29% of the infants developed sPDA, and of them 38% responded to indomethacin treatment. In the expectantly treated group, 37% developed sPDA, and of them 59% responded to indomethacin treatment. Overall, surgical ligation rate for sPDA was similar between both groups of patients. CONCLUSION: In our experience, indomethacin prophylaxis does not show any advantages over expectant early treatment on the management of sPDA in ELBW infants. Although no deleterious effects were observed, prophylaxis exposed a significant number of infants who may have never developed sPDA, to potential indomethacin-related complications.

The effects of indomethacin tocolysis on the postnatal response of the ductus arteriosus to indomethacin in extremely low birth weight infants.

BACKGROUND: Antenal indomethacin reportedly decreases the responses of a symptomatic patent ductus arteriosus (sPDA) to postnatal indomethacin treatment. Whether a similar exposure affects the responses to indomethacin prophylaxis is unknown. OBJECTIVE: To evaluate the clinical responsiveness of ductus arteriosus to indomethacin prophylaxis and to the treatment of sPDA in extremely low birth weight (ELBW) infants following indomethacin tocolysis. METHODS: Retrospective cohort study of 58 ELBW infants whose mothers received indomethacin tocolysis (study) and 58 ELBW infants whose mothers did not (controls), matched by gender, gestational age (GA), birth weight and postnatal sPDA management (prophylaxis or early treatment). RESULTS: Indomethacin was used as a tocolytic at a median dose of 250 mg, for a duration of 2 days, and ending 1 day before delivery. Study and control mothers were comparable in demographics, antenatal steroid use, cesarean delivery, but were different in the incidence of preeclampsia and preterm labor. Study and control infants were similar in birth weight, GA, indomethacin prophylaxis, early sPDA treatment, mortality, necrotizing enterocolitis, severe intraventricular hemorrhage and stage 3-5 retinopathy of prematurity. Seventeen of 43 study and 16 of 43 control infants who received indomethacin prophylaxis developed sPDA and were combined with early treatment sPDA infants (15 to each group). Two of 32 study and two of 31 control infants underwent surgical ligation whereas the remaining were treated with indomethacin. Sixteen of 30 (53%) and 13 of 29 (45%) were successfully treated and did not require ligation. Study infants were divided according to their mothers' indomethacin total dose (28 infants received 225 mg). Both subgroups were demographically and clinically comparable and their response to indomethacin prophylaxis and treatment were similar. CONCLUSION: In ELBW infants, exposure to indomethacin tocolysis does not affect the clinical responsiveness of the ductus arteriosus to prophylaxis or that of the sPDA to indomethacin treatment.

Endothelin ET(A) and ET(B) receptors in postnatal intestine.

We aimed to characterize endothelin (ET) receptors in the swine intestinal vasculature and to determine ischemia-reperfusion (I/R) effects on these receptors. Saturation and competitive binding assays were performed on mesenteric artery protein membranes from 1- and 40-day-old animals, both control and those subjected to 1 h of partial ischemia followed by 6 h of reperfusion in vivo. Scatchard analysis of saturation binding with (125)I-labeled ET-1 in membranes from endothelium-denuded (E(-)) vessels revealed that the maximum number of binding sites was greater in younger animals. Competitive (125)I-ET-1 binding was significant for a one-site model with ET-1, ET-3, and sarafotoxin S6c (S6c) in membranes from endothelium-intact (E(+)) and E(-) vessels in both age groups. The maximum number of ET-1 binding sites was significantly greater in younger animals. In the presence of the ET(A) receptor antagonist BQ-123, competitive (125)I-ET-1 binding was significant for a one-site model with ET-1 and S6c in membranes from E(+) vessels in both age groups. The maximum number of ET-1 binding sites was significantly greater in younger animals. After I/R, the maximum number of ET-1 binding sites was unchanged. In the presence of BQ-123, specific binding by ET-1 and S6c was eliminated in both age groups after I/R. These results suggest that both ET receptor populations are expressed to a greater degree in younger animals and I/R significantly affects the ET(B) receptor.

Determinants of terminal mesenteric artery resistance during the first postnatal month.

Experiments were conducted to delineate the vascular effector systems that contribute to setting mesenteric vascular tone in swine during the first postnatal month. Terminal mesenteric arteries (TMA), which function as resistance vessels, were studied in vitro with a microvascular perfusion system allowing independent pressure and flow manipulation. When pressure was varied 0-100 mmHg in the absence of flow, TMA from 1-day-old animals demonstrated myogenic vasoconstriction, whereas TMA from 40-day-old animals did not. In 1- but not 40-day-old TMA, the endothelin A (ET(A)) receptor antagonist BQ-610 shifted the pressure-diameter curve upward, whereas the ET(B) receptor antagonist BQ-788 and the L-arginine analog N(G)-monomethyl-L-arginine (L-NMMA) shifted the curve downward; in all instances, myogenic vasoconstriction was preserved. Flow eliminated myogenic vasoconstriction in 1-day-old TMA, i.e., diameter increased as a function of pressure. The effect of BQ-610 was lost under flow conditions; however, BQ-788 and N-acyl-L-Trp-3,5-bis-(trifluoromethyl) benzyl ester, an antagonist specific to the substance P neurokinin-1 (NK(1)) receptor, shifted the pressure-diameter curve downward in the presence of flow, whereas L-NMMA restored myogenic vasoconstriction. Adding flow had no effect on the pressure-diameter relationship in 40-day-old TMA. Other blocking agents, including prazosin, losartan, indomethacin, and charybdotoxin, had no effect on the pressure-diameter relationship in either age group under flow or no-flow conditions. Constitutive production of nitric oxide (NO) and endothelin-1 participates in setting resistance in 1-day-old TMA, and important stimulants to NO production include flow and activation of ET(B) and NK(1) receptors. In contrast, 40-day-old TMA act as passive conduits in which the elastic properties of the vessel are the primary determinant of diameter.

Age-dependent changes in the postnatal intestinal microcirculation.

Significant changes occur in intestinal hemodynamics during the transition from fetal to newborn life and then again during the first postnatal month. Most importantly, basal vascular resistance substantially decreases following birth. It then decreases further between postnatal days 1 and 3, plateaus, and then begins a slow, progressive increase between postnatal days 12 and 30. The basal rate of intestinal blood flow mirrors the changes in vascular resistance in an inverse manner. The postnatal changes in vascular resistance appear to be mediated, in large part, by an increase in the constitutive and stimulated production of nitric oxide. Most importantly, the diameter of terminal mesenteric arteries (150-300 microm diameter) in newborn (i.e., 1 day old) swine is determined by three intrinsic vascular control systems: endothelial production of nitric oxide and endothelin, and the inherent myogenic response of vascular smooth muscle. In contrast, these vessels in older subjects (i.e., 35 days old) are primarily passive in nature and fail to demonstrate significant diameter change in response to blockade of endogenous nitric oxide production or endothelin receptors, or applied perturbations of pressure or flow rate. The circulatory physiology of the perinatal and newborn intestine is exceptional when compared to the adult condition inasmuch as several hemodynamic variables change quite dramatically between fetal and neonatal life and during the first postnatal month. The unique hemodynamic conditions that characterize the perinatal and newborn intestine appear to be part of the overall physiological transition that occurs as the fetus, once born, replaces the placenta with his gastrointestinal tract to obtain nutrition. The goal of this review is to describe the circulatory physiology of the perinatal and newborn intestine, with a particular emphasis on those portions of the intestinal microcirculation that have thus far been studied. First, however, it is important to discuss the age-dependent changes that occur within the intestinal circulation during perinatal and early newborn life.

Endothelin-mediated vasoconstriction in postischemic newborn intestine.

We previously suggested that the profound, sustained vasoconstriction noted in 3-day-old swine intestine after a moderate episode of ischemia-reperfusion (I/R) reflects the unmasking of underlying constrictor tone consequent to a loss of endothelium-derived nitric oxide (NO). In this study, we sought to determine whether endothelin-1 (ET-1) was the unmasked constrictor and whether selective loss of endothelial ET(B) receptors, which mediate NO-based vasodilation, participated in the hemodynamic consequences of I/R in newborn intestine. Studies were performed in innervated, autoperfused intestinal loops in 3- and 35-day-old swine. Selective blockade of ET(A) receptors with BQ-610 had no effect on hemodynamics under control conditions; however, when administered before and during I/R, BQ-610 significantly attenuated the post-I/R vasoconstriction and reduction in arteriovenous O(2) difference in the younger group. In 3-day-old intestine, reduction of intestinal O(2) uptake to a level similar to that noted after I/R by lowering tissue temperature had no effect on the response to BQ-610 or ET-1, indicating that the change in response to BQ-610 noted after I/R was not simply consequent to the reduction in tissue O(2) demand. In studies in mesenteric artery rings suspended in myographs, we observed a leftward shift in the dose-response curve for ET-1 after selective blockade of ET(B) receptors with BQ-788 in 3- but not 35-day-old swine. Rings exposed to I/R in vivo behaved in a manner similar to control rings treated with BQ-788 or endothelium-denuded non-I/R rings.