Role of Vitamin D Therapy in Recovery From Early Neonatal Sepsis (Randomized Controlled Trial)
Condition: Importance of Vitamin D Therapy in Treatment of Neonatal Sepsis
MeSH terms: Sepsis; Toxemia; Neonatal Sepsis
Study type: Interventional
Phase: Phase 3

Summary: 
      Neonatal sepsis is still a major cause of morbidity and mortality despite major advances in
      neonatal intensive care units. Early-onset sepsis (EOS) is an infection of the blood acquired
      vertically from the mother and manifests shortly after birth. The objective of this study is
      to assess the vitamin D status in neonates with Early onset sepsis (EOS) and evaluate the
      influence of different doses of vitamin D3 (800 IU/d versus 400 IU/d), in these infants.
    

Detailed description: 
      Subjects:

      This is a randomized controlled trial (RCT) conducted on sixty (66) full term newborns with
      clinical and laboratory findings of early onset of sepsis (EOS) and admitted to the Neonatal
      Intensive Care Unit of El-Demerdash hospital of Ain Shams university and El Ahrar teaching
      hospital in Zagazig.

        -  Inclusion Criteria: full term newborns with clinical and laboratory findings of early
           onset of sepsis (EOS).

        -  Exclusion Criteria: Preterm newborn, NPO neonates , infants with maternal risk factors ,
           such as clinical and/or histological chorioamnionitis, neonates delivered at home
           ,neonates to mothers with premature rupture of membrane, and major congenital
           abnormalities which may be predisposing factors for development of EOS.

      NB: we excluded the dead cases (6 cases) in the final laboratory and clinical relation with
      serum Vitamin D levels after recovery because sepsis caused death to these neonates and
      recovery didn't occur .

      Methods:

      An informed consent was taken from the legal guardian of the newborns participating in the
      study.

      Detailed history taking from all mothers of neonates in the study laying stress on vitamin D
      supplementation during pregnancy, sun exposure in mothers during pregnancy, place and mode of
      delivery. Dietetic history in all included mothers (National Nutrition institute, 2006).
      Clinical evaluation of all newborns for signs of neonatal sepsis.

      All subjects in the study were subjected to the following:

        1. Clinical Examination: General examination including vital data; temperature, pulse,
           respiratory rate, anthropometric measurements including weight and length (Neonatal
           Anthropometry): In all neonates weight (in Kg) was recorded on an electronic weighing
           scale at birth. Length (in cm) was recorded by measuring tape.

           SDS of weight and length was calculated and plotted against appropriate growth curves
           (Tanner et al., 1968).

        2. Laboratory Investigations: Under aseptic conditions venous blood samples was collected
           into sterile blood collection tubes and the following investigations was performed:

             -  A neonatal sepsis screen including: total leukocyte count, absolute neutrophil
                count, platelet count immature to total neutrophil count and C-reactive protein
                (CRP).

             -  Blood samples for complete blood count (CBC) and blood culture. All patients were
                initially assessed according to Newborn Scale of Sepsis.

                  -  A total clinical score less than 10 indicated that the newborn did not have
                     sepsis-a negative predictive value of 97%.

                  -  Any neonate with a total clinical score greater than 10 was considered
                     ''sick,'' possibly with sepsis. A clinical score greater than 10 is also an
                     indicator of the need for further diagnostic evaluation (Gardner, 2008).

             -  Serum 25 (OH) vitamin D levels: was measured by Human Vitamin D ELISA Kit (Qualpro
                diagnostics, INDIA) in all newborns on the first day of sepsis, 25(OH) vitamin D
                levels were classified according to the guidelines of the Endocrine Society to the
                following reference values:

             -  Sufficient >20 ng/ml (>50 nmol/l)

             -  Insufficient 12-20 ng/ml (30-50 nmol/l)

             -  Deficient <12 ng/ml (<30 nmol/l) (Munns et al., 2016).

      Study design : Subjects were classified into three groups :

      GROUP A (conventional dose Vitamin D) those neonates who received a daily dose of oral
      Vitamin D of 400 IU through Ryle or mouth from onset of diagnosis till recovery from sepsis.

      GROUP B (higher dose Vitamin D) those neonates who receiveda daily dose of oral vitamin D of
      800 IU through ryle or mouth from onset of diagnosis till recovery from sepsis.

      GROUP C (Placebo group) those neonates with early onset sepsis who did not receive any
      vitamin D supplementation.

      Patients were matched regarding sepsis score. All 3 groups were treated using strategy of
      sepsis treatment.

        -  Reevaluation of serum Vitamin D levels for all patients on recovery(recovery was
           assessed by Newborn Scale of Sepsis to be less than 10).

        -  Serum Ca and P were measured initially for all patients upon diagnosis of EOS, and on
           discharge upon recovery Normal range of Ca 8.8-11.3mg/dl Normal range P 4.5-6.2 mg/dl

        -  Urinary Ca will be evaluated after two weeks of onset of vitamin D therapy (for patients
           who experience elevation of serum Ca above normal value).

      Type of Study: Randomized controlled study. Study Setting: This study was conducted on sixty
      (66) full term newborns with clinical and laboratory findings of early onset of sepsis (EOS)
      and were admitted to the Neonatal Intensive Care Unit of El-Demerdash hospital of Ain Shams
      university and El Ahrar teaching hospital in Zagazig.

        -  Study Period: The study took place from January 2018 to January 2021.

        -  Study Population: Full term newborns with early onset sepsis.

        -  Sampling Method: random.

        -  Sample Size:

      Using PASS program, setting alpha error at 5% and power at 80%. After reviewing literature,
      no previous similar study has been done before. So assuming that NICU duration for placebo,
      400IU vitamin D and 800 IU vitamin D respectively is 7±2.5, 5.5±2.5, 4±2.5 based on this, the
      needed sample is 20 cases per group (total 60).

      • Ethical Considerations:

        -  The consent was conducted to the legal guardian or the parents of our patients by the
           investigator.

        -  Premature termination of oral vitamin D was mandatory for patients with abdominal
           distension or feeding intolerance.

        -  All data was treated confidentially and was not be allowed except to the principle
           investigator.
    

Intervention name(s): Vitamin D
Intervention type(s): Drug
Intervention description(s): oral supplementation of two different doses
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment